brent e. wisse, md - washington state health care authority · 1/19/2018 · brent e. wisse, md,...

WA - Health Technology Clinical Committee January 19, 2018

Continuous glucose monitoring - update

Clinical Expert

Brent E. Wisse, MD

Associate Professor, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Harborview Medical Center

Seattle, WA

Attending Physician, Harborview Medical Center and

University of Washington Medical Center Seattle, WA

January 2017

Brent E. Wisse, MD, Curriculum Vitae, 020810

1

Brent E. Wisse, MD email: [email protected]

Personal Data: Place of Birth: Pomona, CA Citizenship: USA

Education: 1991-1995 Medical School (MDCM) Class of 1995 McGill University, Faculty of Medicine, Montreal, Quebec, Canada

1987-1991 Graduate Studies Research, Faculty of Science McGill University, Montreal, Quebec 1984-1987 B.Sc. Immunology McGill University, Faculty of Science, Montreal, Quebec Postgraduate Training: 7/1999-6/2001 Fellow Metabolism, Endocrinology and Nutrition, University of Washington

7/1998-6/1999 Fellow Endocrinology and Metabolism, McGill University Hospital Centers,

Montreal, Quebec, Canada Chief Medical Resident, Royal Victoria Hospital, Montreal, Quebec (12/98-6/99)

7/1995-6/1998 Resident Internal Medicine, Royal Victoria Hospital, Montreal, Quebec Faculty Positions Held: 2008- Associate Professor, Division of Metabolism, Endocrinology and Nutrition,

Department of Medicine, University of Washington, Harborview Medical Center, Seattle, Washington

2002-2008 Assistant Professor, Division of Metabolism, Endocrinology and Nutrition,

Department of Medicine, University of Washington, Harborview Medical Center, Seattle, Washington

2001-2002 Acting Instructor, Division of Metabolism, Endocrinology and Nutrition.

University of Washington Hospital Positions Held: 2001- Attending Physician, Harborview Medical Center and University of

Washington Medical Center 2007- Director HMC Glycemic Control Service Honors: 1987 B.Sc. with First Class Honors 1988-91 McGill Major Fellowship, FCAR Fellowship, MRC Fellowship 1992-94 McConnell Award for Academic Achievement in Medicine (three times)

January 2017


2

1992 Leukemia Research Award 1995 MDCM, Dean's Honor List, Cushing Prize 1997 Resident Research Award 1998 Resident Teaching Award 2000 Endocrine Fellows Foundation Grant Current Employment: N/A Medical Certificates: 1998 ABIM, Board Certification in Internal Medicine 2001 ABIM, Board Certification in Endocrinology, Diabetes and Metabolism 2011 ABIM, Re-certification Endocrinology, Diabetes and Metabolism Licenses: Washington State Medical License 1999 US Medical License 1997

Professional Organizations: North American Association for the Study of Obesity 2000 Endocrine Society 2001 Western Society of Clinical Investigation 2007 Teaching Responsibilities: MCBD Block Director, teaching carbohydrate, protein and lipid metabolism Energetics and Homeostasis Block - lecturer Mentorship: First year Endo Fellows clinical research project: (last 5 years) Jean-Jacques Nya-Ngatchou, Jane-Frances Chukwu, Marisela Noorhasan, Jeff Vercollone,

Jennifer Rosenbaum Clinical research projects: Luisa Duran, MD (Fellowship Research Project 2012-2013) Glycemic Control projects (Liz Berggren, Sean McCliment, Rachel Thompson, Scott Binns) Basic science research projects: Carlos Campos, PhD (NCI R21) – post-doc with R. Palmiter BIBLIOGRAPHY: Peer Reviewed Publications:

1. You-Ten EK, Seemayer TA, Wisse B(E) and Lapp WS. Induction of a glucocorticoid sensitive F1 anti-parental mechanism that affects engraftment during graft-versus-host disease. J. Immunol. 1995 Jul; 155(1): 172-180 [OW]

2. Wisse BE, Campfield LA, Marliss EB, Morais JA, Tenenbaum R, Gougeon R. Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women. Am J Clin Nutr. 1999 Sep;70(3):321-30. [OW]

3. Wisse BE, Frayo RS, Schwartz MW, Cummings DE. Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology. 2001 Aug;142(8):3292-301. [OW]

4. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.

January 2017


3

Diabetes. 2001 Aug;50(8):1714-9. [OW] 5. Wisse BE, Schwartz MW. Role of melanocortins in control of obesity. Lancet. 2001 Sep

15;358(9285):857-9.[REV] 6. Wisse BE, Schwartz MW. The skinny on neurotrophins. Nat Neurosci. 2003

Jul;6(7):655-6. [REV] 7. Wisse BE, Schwartz MW, Cummings DE. Melanocortin signaling and anorexia in

chronic disease states. Ann N Y Acad Sci. 2003 Jun;994:275-81. [OW] 8. Wisse BE, Ogimoto K, Morton GJ, Wilkinson CW, Frayo RS, Cummings DE, Schwartz

MW. Physiological regulation of hypothalamic IL-1beta gene expression by leptin and glucocorticoids: implications for energy homeostasis. Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1107-13. [OW]

9. Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004 Nov;15(11):2792-800. [REV]

10. Wisse BE, Ogimoto K, Schwartz MW. Role of hypothalamic interleukin-1beta (IL-1beta) in regulation of energy homeostasis by melanocortins. Peptides. 2006 Feb;27(2):265-73. [OW]

11. Ogimoto K, Harris MK Jr, Wisse BE. MyD88 is a key mediator of anorexia, but not weight loss, induced by lipopolysaccharide and interleukin-1 beta. Endocrinology. 2006 Sep;147(9):4445-53. [OW]

12. Wisse BE, Ogimoto K, Morton GJ, Williams DL, Schwartz MW. Central interleukin-1 (IL1) signaling is required for pharmacological, but not physiological, effects of leptin on energy balance. Brain Res. 2007 May 4;1144:101-6. Epub 2007 Jan 27.[OW]

13. Wisse BE, Ogimoto K, Tang J, Harris MK Jr, Raines EW, Schwartz MW. Evidence that LPS-induced anorexia depends upon central, rather than peripheral, inflammatory signals. Endocrinology. 2007 Nov;148(11):5230-7. Epub 2007 Aug 2. [OW]

14. Klaff LS, Wisse BE. Current controversy related to glucocorticoid and insulin therapy in the intensive care unit. Endocr Pract. 2007 Sep-Oct;13(5):542-9. [REV]

15. Wisse BE, Kim F, Schwartz MW. Physiology. An integrative view of obesity. Science. 2007 Nov 9;318(5852):928-9. [REV]

16. Kim F, Pham M, Maloney E, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, Chait A, Schwartz MW. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1982-8. Epub 2008 Sep 4. [COLL]

17. Blevins JE, Morton GJ, Williams DL, Caldwell DW, Bastian LS, Wisse BE, Schwartz MW, Baskin DG. Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8. Am J Physiol Regul Integr Comp Physiol. 2008 Dec 24. [COLL]

18. Thompson R, Schreuder AB, Wisse BE, Jarman K, Givan K, Suhr L, Corl D, Pierce B, Knopp R, Goss JR. Improving insulin ordering safely: the development of an inpatient glycemic control program. J Hosp Med. 2009 Sep;4(7):E30-5 [OW]

19. Wisse BE, Schwartz MW. Does hypothalamic inflammation cause obesity? Cell Metab. 2009 Oct;10(4):241-2. [REV]

20. Thaler JP, Choi SJ, Sajan MP, Ogimoto K, Nguyen HT, Matsen M, Benoit SC, Wisse BE, Farese RV, Schwartz MW. Atypical protein kinase C activity in the hypothalamus is required for lipopolysaccharide-mediated sickness responses. Endocrinology. 2009 Dec;150(12):5362-72. Epub 2009 Oct 9. [COLL]

21. Thaler JP, Choi SJ, Schwartz MW, Wisse BE. Hypothalamic inflammation and energy homeostasis: resolving the paradox. Front Neuroendocrinol. 2010 Jan;31(1):79-84. Epub 2009 Oct 12. [REV]

22. Chiu HK, Qian K, Ogimoto K, Morton GJ, Wisse BE, Agrawal N, McDonald TO, Schwartz MW, Dichek HL. Mice Lacking Hepatic Lipase Are Lean and Protected against Diet-Induced Obesity and Hepatic Steatosis. Endocrinology. 2010 Jan 7. [COLL]

January 2017


4

23. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance

induced by saturated fatty acids. Choi SJ, Kim F, Schwartz MW, Wisse BE. Am J

Physiol Endocrinol Metab. 2010 Jun;298(6):E1122-30. Epub 2010 Mar 30 [OW[]

24. Central administration of interleukin-4 exacerbates hypothalamic inflammation and

weight gain during high-fat feeding. Oh-I S, Thaler JP, Ogimoto K, Wisse BE, Morton

GJ, Schwartz MW.Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E47-53. Epub 2010

Apr 6 [COLL]

25. Identification of body fat mass as a major determinant of metabolic rate in mice. Kaiyala

KJ, Morton GJ, Leroux BG, Ogimoto K, Wisse BE, Schwartz MW. Diabetes. 2010

Jul;59(7):1657-66. Epub 2010 Apr 2 [OW]

26. Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. German

JP, Wisse BE, Thaler JP, Oh-I S, Sarruf DA, Ogimoto K, Kaiyala KJ, Fischer JD, Matsen

ME, Taborsky GJ Jr, Schwartz MW, Morton GJ.Diabetes. 2010 Jul;59(7):1626-34. Epub

2010 Apr 27 [COLL]

27. Identification of a physiological role for leptin in the regulation of ambulatory activity and

wheel running in mice. Morton GJ, Kaiyala KJ, Fischer JD, Ogimoto K, Schwartz MW,

Wisse BE. Am J Physiol Endocrinol Metab. 2010 Nov 9. [Epub ahead of print] [OW]

28. Leptin activates a novel CNS mechanism for insulin-independent normalization of severe

diabetic hyperglycemia. German JP, Thaler JP, Wisse BE, Oh-I S, Sarruf DA, Matsen

ME, Fischer JD, Taborsky GJ Jr, Schwartz MW, Morton GJ. Endocrinology. 2011

Feb;152(2):394-404. [COLL]

29. Increased energy expenditure and leptin sensitivity account for low fat mass in

myostatin-deficient mice. Choi SJ, Yablonka-Reuveni Z, Kaiyala KJ, Ogimoto K,

Schwartz MW, Wisse BE. Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1031-

7.[OW]

30. The impact of inpatient point-of-care blood glucose quality control testing. Corl DE, Yin

TS, Hoofnagle AN, Whitney JD, Hirsch IB, Wisse BE. J Healthc Qual. 2011 May 17.

[OW] 31. Obesity is associated with hypothalamic injury in rodents and humans. Thaler JP, Yi CX,

Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. J Clin Invest. 2012 Jan 3;122(1):153-62. [COLL]

32. Lipopolysaccharide-induced lung injury is independent of serum vitamin D concentration. Klaff LS, Gill SE, Wisse BE, Mittelsteadt K, Matute-Bello G, Chen P, Altemeier WA.PLoS One. 2012;7(11):e49076[COLL]

33. Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice. Kaiyala KJ, Morton GJ, Thaler JP, Meek TH, Tylee T, Ogimoto K, Wisse BE. PLoS One. 2012;7(8):e41473 [OW]

34. BDNF Action in the Brain Attenuates Diabetic Hyperglycemia via Insulin-Independent Inhibition of Hepatic Glucose Production. Meek TH, Wisse BE, Thaler JP, Guyenet SJ, Matsen ME, Fischer JD, Taborsky GJ Jr, Schwartz MW, Morton GJ. Diabetes. 2012 Dec 28 [COLL]

35. In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue. Matsen ME, Thaler JP, Wisse BE, Guyenet SJ, Meek TH, Ogimoto K, Cubelo A, Fischer JD, Kaiyala KJ, Schwartz MW, Morton GJ. Am J Physiol Endocrinol Metab. 2013 Apr 1;304(7):E734-46 [COLL]

January 2017


5

36. Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE, Schwartz MW. Diabetes. 2013 Aug;62(8):2629-34. [REV]

37. Evaluation of point-of-care blood glucose measurements in patients with diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care unit. Corl DE, Yin TS, Mills ME, Spencer TL, Greenfield L, Beauchemin E, Cochran J, Suhr LD, Thompson RE, Wisse BE. J Diabetes Sci Technol. 2013 Sep 1;7(5):1265-7 [OW]

38. Efficacy of DNET program to improve nursing confidence and expertise in caring for hospitalized patients with diabetes mellitus. Corl DE, McCliment S, Thompson RE, Suhr LD, Wisse BE. JNPD 2014 May-Jun;30(3):134-42 [OW]

39. Point-of-care blood glucose measurement errors overestimate hypoglycemia rates in critically ill patients. Nya-Ngatchou JJ, Corl D, Onstad S, Yin T, Tylee T, Suhr L, Thompson RE, Wisse BE. Diabetes Metab Res Rev. 2015 Feb;31(2):147-54 [OW]

40. Point-of-care blood glucose measurement in critically ill patients. Corl D, Greenfield L, Hoofnagle A, Baird GS, Suhr LD, Wisse BE. Critical Care Nursing 2015 (in press) [OW]

41. Perioperative Glycemic Control During Colorectal Surgery. Thompson RE, Broussard EK, Flum DR, Wisse BE. Curr Diab Rep. 2016 Mar;16(3):32 [OW]

Daniel Lessler, MDChief Medical Officer, WA – Health Care Authority

January 19, 2018

WA ‐ Health Technology Clinical Committee 1

Continuous glucose monitoring ‐ update

Agency medical director comments

Daniel Lessler, MD, Chief Medical Officer

Washington Health Care Authority

January 19, 2018

Continuous glucose monitoring ‐ Update


Continuous Glucose Monitoring (CGM)

CGM results provide real‐time information about glucose levels that, when correlated with physical activity, diet, and insulin dose, may enable better blood glucose control in patients with diabetes

2


January 19, 2018



• Continuous glucose monitoring systems (CGM) measure glucose in interstitial fluid

• Three components:

– Glucose sensor, inserted subcutaneously

– Transmitter

– Receiver (type of monitor)

• Allows measurement of interstitial glucose every few minutes

– Interstitial glucose correlates well with plasma glucose

– CGM BG‐levels lag plasma levels

• Flash CGM (FCGM) – no passive alerts; data/alert only if sensor scanned

3



• Update to 2011 report which focused on self‐monitoring of blood glucose (SMBG) in those 18 years old or younger who require insulin

• Update includes real‐time continuous glucose monitoring in persons of any age with type 1 or type 2 DM; and, women with diabetes during pregnancy (pre‐existing or gestational)

4



January 19, 2018



Agency Medical Director Concerns

• SAFETY = Medium

• EFFICACY = High

• COST = High


Key Questions

In persons with DM:

1. What is the evidence of efficacy and effectiveness of continuous monitoring?

2. What is the evidence of the safety of continuous glucose monitoring?

3. What is the evidence that glucose monitoring has differential efficacy or safety issues in subpopulations?

4. What is the evidence of cost‐effectiveness of continuous glucose monitoring?

6


January 19, 2018



PICO Scope: Inclusion Criteria

• Population: Persons with DM; type 1, type 2, pregnant women with pre‐existing diabetes or gestational diabetes

• Intervention: FDA‐approved continuous glucose monitoring devices and FDA‐approved combination devices integrating real‐time continuous glucose monitoring with insulin pump/infusion

• Comparators: Self‐monitoring using conventional blood glucose meters, attention control, blinded or sham CGM and usual care

7


• CGM ‐‐ $1000 ‐ $2000 for device

• Sensors and other supplies $350‐$450 per month (though prices for supplies for newer devices are less)

8

CGM Costs


January 19, 2018


Continuous glucose monitoring ‐ update 9

Annual Unique Patients 256 332 456 618

Proc Code

HCPCSDescription 2013 2014 2015 2016 TOTAL

A9276

SENSOR; INVASIVE (E.G.

SUBCUTANEOUS), DISPOSABLE, FOR

USE WITH INTERSTITIAL GLUCOSE

MONITORING

$183,610 $351,509 $570,434 $824,323 $1,929,876

A9277TRANSMITTER; EXTERNAL, FOR USE

WITH INTERSTITIAL CONTINUOUS

GLUCOSE MONITORING $46,396 $78,605 $122,773 $185,850 $433,624

A9278RECEIVER (MONITOR); EXTERNAL,

FOR USE WITH INTERSTITIAL

CONTINUOUS GLUCOSE $19,337 $22,884 $37,796 $57,752 $137,769

Grand Total $249,343 $452,998 $731,003 $1,067,925 $2,501,269

2013 ‐2016 PEBB/ UMP

Paid Dollars by Year for CGM and Related Items

(CPT/HCPCS)

Continuous glucose monitoring ‐ update 10

Proc Code –

HCPCSDescription 2014 2015 2016 Total

A9276 SENSOR $719,681 $1,927,402 $3,255,554 $5,902,637

A9277 TRANSMITTER $207,403 $347,211 $725,258 $1,279,872

A9278 RECEIVER $67,185 $108,193 $250,292 $425,670

Grand Total $994,269 $2,382,806 $4,231,104 $7,608,179

2014 ‐2016 Medicaid MCO

Paid Dollars by Year for CGM and Related Items (CPT/HCPCS


January 19, 2018



Overall Summary: CGM in People with Type 1 DM

• Children and Adolescents (<18 yo): CGM improves HbA1C control short term (3 months), without worsening hypoglycemia; some evidence of improvement in HbA1C at 6 months (e.g. more recent cross‐over trial, Battelino et al, 2012.)

• In adults, CGM improves HbA1C control up to 1 year, without worsening hypoglycemia

• In adults, CGM reduces the time spent with “biochemical” hypoglycemia at 3 and 6 months

11


Overall Summary: CGM in Adults with Type 2 DM

• Improvement in HbA1C control at 3 and 6 months

• No difference in minutes per day spent with “biochemical” hypoglycemia (BG < 70 mg/dl)

12


January 19, 2018



CGM in Pregnancy

• Pre‐existing Type 1 diabetes– Decreases C‐section rate

– Decreases admission to NICU– No effect on time spent in hypoglycemia

• Pre‐existing Type 2 diabetes– Insufficient evidence to evaluate differences in outcome

between CGM and SMBG (1 small trial)

• Gestational diabetes– Insufficient evidence to evaluate differences in outcome

between CGM and SMBG (1 small trial)

13


“Flash” CGM Evidence

• Strength of evidence insufficient for “Flash” CGM

– Available data insufficient to determine effect on HbA1C control (1 study showed no difference)

– Available data insufficient to determine effect on hypoglycemia (1 study associated with less time spent in hypoglycemic range <55 mg/dl)

14


January 19, 2018



CGM Safety

• Most common adverse effects include skin related reactions/irritation that are generally not serious

• More serious adverse events include cellulitis and skin abscess, relatively rare across 9 trials (0% ‐ 9%)

• Device malfunction (including those that are sensor related) is the other category of safety related adverse events

– Wide variability in clinical trials

– The overall incidence of device malfunction related adverse events is not known as numbers of CGM sold and operating is unknown

– Nature of reporting varies across manufacturers (i.e. reporting not standardized)*

* Diabetologia (2017) 60:2319‐2328

15


Important Context• Most trials conducted in “efficacy” context; “real world”

outcomes may differ

• Which patients may benefit most from CGM is unclear

– Available data suggests importance of patient regularly using the device (e.g. “most days” of the week)

– Role of patient motivation, education, self‐management plan and reinforcement/follow‐up not well defined

• Longer term studies (>1 year) of the impact of CGM on HbA1C control and hypoglycemia are lacking

• No long term data on disease outcomes– Given the length of time and number of patients required for such

studies, and the known relationship between HbA1C and clinical outcomes, HbA1C appears to be a reasonable surrogate

• Rapidly changing technology that out paces evaluative studies16


January 19, 2018



CGM: Cost‐Effectiveness

• Available CE models show wide range of results, depending on assumptions

• With favorable assumptions, CGM appears cost‐effective for Type 1 DM and Type 2 DM, assuming willingness to pay <$100,00/QALY

17


CGM Clinical Guidelines: National Organizations

• Endocrine Society ‐ Children

– Recommends RT‐CGM be used by children and adolescents with T1DM who have achieved HbA1C levels below 7.0% b/c it will assist in maintaining target HbA1C levels while limiting the risk of hypoglycemia

– Recommends RT‐CGM for children and adolescents with T1DM who have HbA1C levels > 7.0% and are able to use devices on a near daily basis

– No recommendation for or against the use of RT‐CGM by children with T1DM who are < 8 y.o.

18


January 19, 2018




• Endocrine Society – Adults

– RT‐CGM is recommended for adult patients with T1DM who have A1C levels above target and who are willing and able to use devices on a nearly daily basis

– RT‐CGM is recommended for adult patients with well‐controlled T1DM who are willing and able to used devices on a nearly daily basis

– It is suggested that short‐term intermittent RT‐CGM is used in adult patients with T2DM (not on prandial insulin) who have HbA1C levels > 7.0% and are willing and able to use the device

19



• American Association of Clinical Endocrinologists and American College of Endocrinology

– CGM should be considered for patients with T1DM and T2DM on intensive insulin therapy to improve A1C levels and reduce hypoglycemia

– CGM may benefit patients not taking insulin

20


January 19, 2018




• Endocrine Society 2013 – Diabetes and pregnancy

– CGM is suggested for use during pregnancy in women with overt or gestational diabetes when self‐monitored glucose levels (or HbA1C values in women with overt diabetes) are not sufficient to assess glycemic control

21


Medicare National Coverage Decision

• “Non‐Therapeutic” CGMs that are used as an adjunct to BGM (i.e. therapeutic decisions regarding diabetes treatment must be made with standard home BGM, not the CGM) are NOT covered as DME

• “Therapeutic CGMs,” defined as a CGM used as a replacement for fingerstick glucose testing are covered as DME for patients with diabetes who have been performing SMBG > 4X/day and is insulin treated with multiple daily injections or continuous infusion pump

– Dexcom G5 and FreeStyle Libre are currently the only FDA‐approved devices with a therapeutic (or “non‐adjunctive”) indication

22


January 19, 2018



CGM: Commercial Insurance Coverage Policies

• Kaiser Washington

– Covered for people with type 1 and type 2 diabetes who, despite adherence to an appropriate glycemic management plan (customized basal‐bolus insulin regimen; testing BG 4 > per day; competent problem‐solving skills; carbohydrate counting and appropriate meal management) have:

• History of hypoglycemia unawareness within the past 3 yrs resulting in frequent and severe hypoglycemia; or

• History within the past 3 yrs of frequent and severe hypoglycemia

• Request must be made by an endocrinologist

23


• Blue Cross – Blue Shield

– CGM may be considered medically necessary for:

• Patients with type 1 DM who have demonstrated an understanding of the technology, are motivated to use the device, are expected to adhere to a comprehensive DM rx plan supervised by a qualified provider, and are capable of using the device to recognize alerts and alarms, or

• Patients with type 1 DM who have recurrent, unexplained hypoglycemia (BG < 50 mg/dl), or impaired hypoglycemia awareness

• Patients with poorly controlled type 1 DM who are pregnant

24

CGM: Commercial Insurance Coverage Policies


January 19, 2018



• Continuous glucose monitoring (CGM) is a covered benefit for diabetes mellitus (DM) patients under 19 using insulin when the following conditions are met:

– Suffering from one or more severe episodes of hypoglycemia

– Enrolled in an IRB approved trial

25

HTCC 2011: Glucose Monitoring for Insulin Dependent Individual Under 19 Years of Age


AMDG CGM Recommendation: Children/Adolescents < 19 y.o.

• Continuous glucose monitoring (CGM) is a covered benefit for children/adolescents under 19 with Type 1 diabetes when the following conditions are met:

– Unable to achieve target HbA1C despite adherence to an appropriate glycemic management plan (intensive insulin therapy; testing BG 4 or more times per day); OR

– Suffering from one or more severe (BG < 50 mg/dl or symptomatic) episodes of hypoglycemia despite adherence to an appropriate glycemic management plan (intensive insulin therapy; testing BG 4 or more times per day) ; OR

– Inability to recognize, or communicate about, symptoms of hypoglycemia


January 19, 2018



AMDG CGM Recommendation: Adults Type 1 Diabetes

• Continuous glucose monitoring (CGM) is a covered benefit for adults with type 1 diabetes patient when the following conditions are met:– Unable to achieve target HbA1C despite adherence to an appropriate

glycemic management plan (intensive insulin therapy; testing BG 4 or more times per day); OR

– Suffering from one or more severe (BG < 50 mg/dl or symptomatic) episodes of hypoglycemia despite adherence to an appropriate glycemic management plan (intensive insulin therapy; testing BG 4 or more times per day) ; OR


27


AMDG CGM Recommendation: Adults Type 2 Diabetes

• Continuous glucose monitoring (CGM) is a covered benefit for adults with type 2 diabetes patient when the following conditions are met:– Unable to achieve target HbA1C despite adherence to an appropriate

glycemic management plan (intensive insulin therapy; testing BG 4 or more times per day); OR

– Suffering from one or more severe (BG < 50 mg/dl or symptomatic) episodes of hypoglycemia (intensive insulin therapy; testing BG 4 or more times per day) ; OR


28


January 19, 2018



• Covered for pregnant women with type 1 diabetes;

• Covered for pregnant women with type 2 diabetes on insulin prior to pregnancy;

• Covered for pregnant women with type 2 diabetes whose BG does not remain well controlled (HbA1C above target or experiencing episodes of hyperglycemia or hypoglycemia) on diet and/or oral medications during pregnancy and require insulin;

• Covered for pregnant women with gestational diabetes whose blood sugar is not well controlled (HbA1C above target or experiencing episodes of hyperglycemia or hypoglycemia) during pregnancy and require insulin

29

AMDG CGM Recommendation: Pregnant Women with Diabetes


AMDG Recommendation: Flash CGM

• CGM with a “flash” device is not covered

30


January 19, 2018



Questions?

More Information:

[email protected]

WA – Health Technology Clinical Committee January 19, 2018

Order of scheduled presentations

Continuous glucose monitoring – update

Name Affiliation

1 Tomas Walker, MD Dexcom

2 Catherine Pihoker, MD Seattle Children’s Hospital

3 Amy Bronstone, PhD AB Medical Communications

4 Molly Carlson, MD Division of Endocrinology, University of Washington School of Medicine

5 Refaat Hegazi Abbott Diabetes Care

6 Zoe Alfaro

7 Richard Hellmund Abbott Diabetes Care

8 Irl Hirsch, MD University of Washington School of Medicine

WA – Health Technology Assessment

Page 2 of 2 conflict_of_interest_121814-FINAL.docx

Disclosure

Any unmarked topic will be considered a “Yes”

Potential Conflict Type Yes No

1. Salary or payments such as consulting fees or honoraria in excess of $10,000.

2. Equity interests such as stocks, stock options or other ownership interests.

3. Status or position as an officer, board member, trustee, owner.

4. Loan or intellectual property rights.

5. Research funding.

6. Any other relationship, including travel arrangements.

If yes, list name of organizations that relationship(s) are with and for #6, describe other relationship:

_________________________________________________________________________________

_________________________________________________________________________________

________________________________________________________________________________________


7. Representation: if representing a person or organization, include the name and funding sources (e.g. member dues, governmental/taxes, commercial products or services, grants from industry or government).

If yes to #7, provide name and funding Sources: _________________________________________________

_________________________________________________________________________________

________________________________________________________________________________________

________________________________________________________________________________________

If you believe that you do not have a conflict, but are concerned that it may appear that you do, you may attach additional sheets explaining why you believe that you should not be excluded.

I certify that I have read and understand this Conflict of Interest form and that the information I have provided is true, complete, and correct as of this date.

Signature Date Print Name

So we may contact you regarding your presentation, please provide the following:

Email Address:

Phone Number:

XX

XXX

X

I am an employee of and stockholder in Dexcom , Inc.

X

I am an employee of and stockholder in Dexcom, Inc manufacturer of the Dexcom G5 MobileContinuous Glucose Monitoring system.

twalker @dexcom.com

+1 - 858-886-9247

Tomas C Walker, DNP, APRN

I am the Senior US Medical Director for Dexcom, Inc.

18 Dec 2017

Tomas Walker, MDU.S. Senior Medical Director, Dexcom

January 19, 2018


1. CGM has evolved 4 generations since 2007

2. Accuracy, reliability, and performance are all significantly improved

– CGM today is recognized as reliable and accurate enough to replace fingersticks for routine decision making

3. Health technology assessments should focus on current clinical trials with technology available today

– Not pooling discontinued and current devices

Meta-Analyses are Inappropriate Tools for Evolving Technology

Price, D., Graham, C., Parkin, C. G., & Peyser, T. A. (2016). Are systematic reviews and meta-analyses appropriate tools for assessing evolving medical device technologies?. Journal of diabetes science and technology, 10(2), 439-446.

Significant Evolutions in Performance

• Rapid evolution renders meta-analysis difficult

• Previous generations of technology are no longer available

Tomas Walker, MDU.S. Senior Medical Director, Dexcom

January 19, 2018


Remote MonitoringAllows parents or caregivers to monitor glucose remotely

Does Remote Monitoring Impact Care?

136 327 1291 1052 931 774

0

5

10

15

20

25

30

0%

5%

10%

15%

20%

25%

0 1 2 3 4 5

Utilization (days / m

onth)

%<7

0 m

g/dL

Number of Followers

% <70 mg/dL

Utilization

Number of sharers in each "Followers" category

N=4511, Aged 2-10yoParker AS, Welsh JB, Hutchings M, Jimenez A, Walker T. Hypoglycemic exposure among children using the Dexcom Share Cloud. Poster presented at: Diabetes Technology Meeting; November 2, 2017; Bethesda, MD.

Cate Pihoker, MD January 19, 2018


CGM Use Is Increasing But Still Low

4% 4% 3% 4%

15% 16%10%

49%

32%

20% 21%

37%35%

24%

0%

10%

20%

30%

40%

50%

<6 6-<13 13-<18 18-<26 26-<50 50-<65 ≥ 65

Age (years)

Enrolled 2010-2012 (7% use CGM overall)

Current 05/01/2016-07/31/2017 (28% use CGM overall)

CGM Use by Insulin Delivery Method

64%

42%

28% 28%

46% 47%

31%27%

14%8% 10%

18%15% 13%

0%

10%

20%

30%

40%

50%

60%

70%

<6 6-<13 13-<18 18-<26 26-<50 50-<64 ≥ 65

Age (years)

Pump Injection



Lower HbA1c in CGM Users

8.7%

9.2%

7.9%7.9%

8.4%

7.4%

7.0%

7.5%

8.0%

8.5%

9.0%

9.5%

<13 13-<26 ≥26

Mea

n H

bA1c

%

Age, years

Non CGM Users CGM Users

Lower HbA1c in CGM Users Across Races/Ethnicities

8.5%

7.8%

9.9%

8.7%9.1%

8.1%

6.0%6.5%7.0%7.5%8.0%8.5%9.0%9.5%

10.0%10.5%

non-CGM CGM non-CGM CGM non-CGM CGM

African-AmWhite Hispanic



HbA1C by CGM use by age group

7.4

7.6

7.8

8

8.2

8.4

8.6

8.8

9

Age < 6 yr Age 6-12 yr Age > 12 yr

no CGM CGM daily

HbA1C by CGM use by age group

7.4

7.6

7.8

8

8.2

8.4

8.6

8.8

9


no CGM CGM daily



Lower HbA1C at Seattle Children’s, by age group

7.2

7.4

7.6

7.8

8

8.2

8.4

8.6

8.8

9

9.2


no CGM CGM daily CGM sometimes



Disclosure

Any unmarked topic will be considered a “Yes”


1. Salary or payments such as consulting fees or honoraria in excess of $10,000.

2. Equity interests such as stocks, stock options or other ownership interests.

3. Status or position as an officer, board member, trustee, owner.

4. Loan or intellectual property rights.


6. Any other relationship, including travel arrangements.

If yes, list name of organizations that relationship(s) are with and for #6, describe other relationship:

_________________________________________________________________________________

_________________________________________________________________________________

________________________________________________________________________________________




_________________________________________________________________________________

________________________________________________________________________________________

________________________________________________________________________________________


I certify that I have read and understand this Conflict of Interest form and that the information I have provided is true, complete, and correct as of this date.

Signature Date Print Name


Email Address:

Phone Number:

xxxx

xx

I provide consulting services to Dexcom, Inc.

x

Dexcom, Inc.

12-19-2017 Amy Bronstone

[email protected]

510-381-2498

Amy Bronstone, PhDAB Medical Communications

January 19, 2017


People with insulin-treated diabetes who have impaired awareness of hypoglycemia (IAH)

Enrollees with Diabetes(107,170)

Target Population

Enrollees with Insulin-treated Diabetes(34,756)

Enrollees with Insulin-treated Diabetes with IAH(4464)

Model Parameters

Annual cost of CGM per patient: $2800

Amy Bronstone, PhDAB Medical Communications

January 19, 2017


Annual cost of severe hypoglycemic events

Annual Cost of Severe Hypoglycemic Events Requiring Emergency Treatment

Net cost of emergency treatment for severe hypoglycemia$39,029,180 - $28,507,629 =

Cost Savings: $10,521,551



Disclosure Any unmarked topic will be considered a “Yes”

Potential Conflict Type Yes No 1. Salary or payments such as consulting fees or honoraria in excess of $10,000. 2. Equity interests such as stocks, stock options or other ownership interests. 3. Status or position as an officer, board member, trustee, owner. 4. Loan or intellectual property rights.


6. Any other relationship, including travel arrangements. If yes, list name of organizations that relationship(s) are with and for #6, describe other relationship: _________________________________________________________________________________

_________________________________________________________________________________

________________________________________________________________________________________




_________________________________________________________________________________ ________________________________________________________________________________________

________________________________________________________________________________________


I certify that I have read and understand this Conflict of Interest form and that the information I have provided is true, complete, and correct as of this date. X Signature Date Print Name


Email Address:

Phone Number:

Yes

Yes

I am a part of the Dexcom ambassador program, Dexcom Warriors. With this relationship I help to spread diabetes awareness and education. I am disclosing that my travel arrangements have been paid by Dexcom for this meeting.

No

No

No

No

No

Dexcom, no funding sources applicable.

Zoe Alfaro

Dec 20 2017

Zoe Alfaro

[email protected]

707-225-1398


Applicant Name Irl Hirsch

Address 14310 SE 63rd St Bellevue, WA 98006

1. Business Activities

(a) If you or a member of your household was an officer or director of a business during the immediately preceding calendar year and the current year to date, provide the following:

Title Business Name & Address Business Type

(b) If you or a member of your household did business under an assumed business name during the immediately preceding calendar year or the current year to date, provide the following information:

Business Name Business Address Business Type

2. Honorarium and Research Funding

If you received an honorarium of more than $100 during the immediately preceding calendar year and the current year to date, list all such honoraria:

Received From Organization Address Service Performed

Abbott Diabetes Care 1360 S Loop Rd, Alameda, CA 94502 Consultant

Roche

9115 Hague Road PO Box 50457 Indianapolis, IN 46250 Consultant

BigFoot 1561 Buckeye Drive Milpitas, CA 95035 Consultant

Adocia

115 avenue Lacassagne 69003 Lyon France Consultant

Medtronic Diabetes 18000 Devonshire Street, Northridge, CA 91325 Research funding to UW

Page 2 of 5

WA – Health Technology Assessment 3. Sources of Income

(a) Identify income source(s) that contributed 10% or more of the combined total gross household income received by you or a member of your household during the immediately preceding calendar year and the current year to date.

Source Name & Address Received By Source Type

(b) Does any income source listed above relate to, or could it reasonably be expected to relate to, business that has, or may, come before the Committee?

☐ Yes ☐ No

If “yes”, describe:

(c) Does an income source listed above have a legislative or administrative interest in the business of the Committee?

☐ Yes ☐ No

If “yes”, describe:

4. Business Shared With a Lobbyist

If you or a member of your household shared a partnership, joint venture, or similar substantial economic relationship with a paid lobbyist, were employed by, or employed, a paid lobbyist during please list the following:

(Owning stock in a publicly traded company in which the lobbyist also owns stock is not a relationship which requires disclosure.)

Lobbyist Name Business Name Type Business Shared

Page 3 of 5


Provide the information requested in items 5, 6, and 7 below only if: (a) Your response involves an individual or business if you or a member of your household did business with, or reasonably could be expected to relate to business that has or may come before the Health Technology Clinical Committee. (b) The information requested involves an individual or business with a legislative or administrative interest in the Committee.

5. Income of More Than $1,000

List each source (not amounts) of income over $1,000, other than a source listed under question 3 above, which you or a member of your household received during the immediately preceding calendar year and the current year to date:

Income Source Address Description of Income Source

6. Business Investments of More Than $1,000

(Do not list the amount of the investment or include individual items held in a mutual fund or blind trust, a time or demand deposit in a financial institution, shares in a credit union, or the cash surrender value of life insurance.)

If you or a member of your household had a personal, beneficial interest or investment in a business during the immediate preceding calendar year of more than $1,000, list the following:

Business Name Business Address Description of Business

7. Service Fee of More Than $1,000

(Do not list fees if you are prohibited from doing so by law or professional ethics.)

List each person for whom you performed a service for a fee of more than $1,000 in the immediate preceding calendar year or the current year to date.

Name Description of Service

I certify that I have read and understand this Conflict of Interest Form and the information I have provided is true and correct as of this date.

Print Name Irl Hirsch

Page 4 of 5


Check One: ☐ Committee Member ☐ Subgroup Member ☒ Contractor

12/21/2017

Signature Date

C:\Users\kylat2\Desktop\coi_member_hard_copy-B.docx Page 5 of 5

Irl B. Hirsch, MDProfessor of Medicine, University of Washington

January 19, 2018


Understanding CGM in 2018

Irl B. Hirsch, MD

Professor of Medicine

University of Washington School of Medicine

5 97 (76-120)

6 126 (100-152)

7 154 (123-185)

8 183 (147-217)

9 212 (170-249)

10 249 (192-282)

11 269 (217-314)

12 298 (240-347)

Average Glucose Versus A1C

A1C (%) AG (mg/dL [95% CI])

Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ. Diabetes Care. 2008;31:1473-1478.

Historically, HbA1c has been our treatment target for the past 35

years. Is that appropriate? Is it safe?


January 19, 2018


Hypoglycemia as the Cause of Death in Pediatric and Young Adult Type 1 Diabetes

This is not a benign problem!

Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G. Diabetologia. 2006:49:298-305. Feltbower RG, Bodansky HJ, Patterson CC, et al. Diabetes Care. 2008;31:922-926.Patterson CC, Dahlquist G, Harjutsalo V, et al. Diabetologia. 2007;50:2439-2442.JAMA 2015;313:45-53

0

2

4

6

8

10

12

Skrivarhaug Feltbower Patterson DCCT/EDIC

Per

cent

age

of A

ll M

orta

lity

Frequency of Severe Hypoglycemia*Related to Type 1 Diabetes Duration

*Seizure or coma

Age, years

Per

cent

/Yea

r

Weinstock RS, Xing D, Maahs DM, et al. J Clin Endocrinol Metab. 2013;98:3411-3419.

Given the limitations of HbA1c, and the dangers of hypoglycemia in both T1D and T2D taking insulin, wouldn’t it make more sense to treat the glucose instead of the HbA1c?


January 19, 2018


CGM Use Is Increasing in the T1D Exchange

4% 4% 3% 4%

15% 16%10%

49%

32%

20% 21%

37%35%

24%

0%

10%

20%

30%

40%

50%

<6 6‐<13 13‐<18 18‐<26 26‐<50 50‐<65 ≥ 65

Age (years)

Enrolled 2010‐2012 (7% use CGM overall)

Current 05/01/2016‐07/31/2017 (28% use CGM overall)

Before Medicare coverage

UW DCC 1/18: > 60% (AFL)

Lower HbA1c in CGM Users (N=16,656)

8.7%

9.2%

7.9%7.9%

8.4%

7.4%

7.0%

7.5%

8.0%

8.5%

9.0%

9.5%

<13 13-<26 ≥26

Mea

n H

bA1c

%

Age, years

Non CGM Users CGM Users


January 19, 2018


My UW Clinic, Jan 3, 2018

• 14 patients, 10 T1D, 3 T2D, 1 steroids after transplant

• CGM: 7/10 T1D, 1/3 T2D: 8/14 total

• First two patients: complete hypo unawareness. One 51y/o M, the other 71y/o M; both of them without a SH wearing CGM (total 12 yrs)

Take Home Points

•We treat the glucose, not the HbA1c

•“For every complex problem there is an answer that is clear, simple, and wrong” (HL Menckin)•Diabetes, especially type 1 diabetes is complex, and NOT having access to CGM in 2018 is wrong

Andrea C. Skelly, PhD, MPHAggregate Analytics, Inc.

January 19, 2018


Continuous Glucose Monitoring Re‐ReviewPresentation to

Washington State Health Care Authority

Health Technology Clinical Committee

Andrea C. Skelly, PhD, MPHJanuary 19, 2018

Report prepared by: Andrea C. Skelly, PhD, MPH

Erika D. Brodt, BSCassandra Winter, BSAaron Ferguson, BSNaomi Schwartz, BA

Mark Junge, BS

1

Scope, Update to 2011 Report • 2011 Report: self‐monitoring of blood glucose (SMBG) and real‐

time continuous glucose monitoring (CGM) in those 18 years old or younger who require insulin

• Update report:

– Focus on real‐time continuous glucose monitoring (CGM) in persons of any age group with diabetes mellitus (T1 or T2); women with diabetes during pregnancy (pre‐existing or gestational)

– Technological improvements in CGM technology; more widespread use

– Insulin delivery (pumps vs. injections) not part of scope

2


January 19, 2018


Background ‐ Diabetes Types

• Diabetes mellitus (DM) is a serious chronic condition for which there is no definitive cure.

• DM is categorized into 3 major types, based on etiology

– Type 1 (T1DM): is an autoimmune disorder that destroys pancreatic beta cells which make insulin. It is the most common form in persons ≤ 18 years old. Insulin therapy is required.

– Type 2 (T2DM): Is most common in adults, is caused by insulin resistance, disordered and inadequate insulin release and excessive glucose production by the liver. Diet, exercise and oral medications may be effective in the first years; however, it is progressive and insulin therapy may eventually be required.

– Gestational (GDM): defined as glucose intolerance with pregnancy onset/first recognition of pregnancy.

3

Background‐Diabetes Complications• Chronic complications are strongly related to DM duration and

glycemic control (T1 and T2DM): – Macrovasculsar complications (e.g. heart disease, stroke)

– Microvascular complications (retinopathy, nephropathy, neuropathy)

– Increased risk of infection, cancer, other autoimmune disorders (e.g. celiac sprue, thyroid disease)

• Hypoglycemia: 3 X more common in children (vs. adults), may be difficult to detect (unawareness); can damage brain, lead to seizures, coma, death; Severe hypoglycemia – rare event, generally in T1DM

• Diabetic ketoacidosis (DKA): severe hyperglycemia; leading cause of hospitalizations in children with T1DM nationally; can lead to coma, death

4


January 19, 2018


Background• DM duration is associated with chronic complications, thus, younger

persons may have the most to gain from maintaining good glycemic control yet have some of the greatest challenges in achieving and

maintaining it.

• Goal: Achieve/maintain glucose and A1C levels as close to normal as possible while minimizing episodes of severe hypoglycemia

• Intensive management with tight control has become standard of care. Glucose monitoring plays an integral part:

– Provides data for decision making

– Assists in identifying and preventing hypoglycemia

– Provides “peace of mind” to care givers

– Influences activities and quality of life

5

Self‐monitoring of blood glucose (SMBG)(intermittent monitoring)

• First FDA approval 1975

• Capillary blood drop placed on reagent‐impregnated paper strips; monitor reads

• Provides “snap shot” of blood glucose levels

• Recommended: at least 4 times/day; individualized

• Barriers, adherence, use of data

6


January 19, 2018


Traditional Real‐time Continuous Glucose Monitor (TCGM)

• Subcutaneously placed, enzyme‐embedded sensor samples interstitial fluid glucose; connected to transmitter

• Glucose data sent continuously to a receiver or smartphone app

• “Real‐time” view of glucose level changes and trend information

• Threshold alarms for high, low glucose levels

• May be used with insulin pump (sensor augmented pump therapy)

• SMBG for calibration

http://www.nbdiabetes.org/news/continuous‐glucose‐monitoring‐system‐cgms

https://www.niddk.nih.gov/health‐information/diabetes/overview/managing‐diabetes/continuous‐glucose‐monitoring

7

Flash “Continuous” Glucose Monitor (FCGM)

• Sensor (upper arm only) samples interstitial fluid glucose every minute; stores 8 hours of data

• Sensor must be scanned by separate reader; data are notcontinuously sent, no connectivity with mobile devices/smart phones

• No passive alerts; data, alerts, trends only if sensor scanned

• FDA approval >18 year olds only

• SMBG not required for calibration, treatment decisions

http://www.nbdiabetes.org/news/continuous‐glucose‐monitoring‐system‐cgms

https://www.healthline.com/diabetesmine/newsflash‐fda‐oks‐freestyle‐libre‐united‐states#2

8


January 19, 2018


Real‐time Continuous Glucose Monitor (CGM)

• Advances in traditional CGM technology:

o Enhanced accuracy and precision

o Timeliness and display of alarms (visual, audible)

o Increased sensor durability, wear time; decreased size

• Some devices require SMBG for verification (adjunctive)

• Therapeutic device: replacement for fingerstick BG testing for treatment decisions (i.e. used as a primary system and not as an adjunct)

o DexCom G5 Mobile CGM, Medtronic MiniMed 670G automates insulin delivery based on CGM);

o SMBG required for calibration; may be recommended

• Patient education, support, adherence are important

• Flash GM differs from traditional CGM

9

Key QuestionsIn persons with diabetes mellitus (DM):



3. What is the evidence that glucose monitoring has differential efficacy or safety issues in subpopulations?

4. What is the evidence of cost‐effectiveness of continuous glucose monitoring?

10


January 19, 2018


PICO Scope: Inclusion Criteria• Population: Persons with diabetes mellitus; type 1, type

2, pregnant women with pre‐existing diabetes or gestational diabetes

• Interventions: FDA‐approved real‐time continuous glucose monitoring devices and FDA‐approved combination devices integrating real‐time continuous glucose monitoring with insulin pump/infusion

• Comparators: Self‐monitoring using convention blood glucose meters, attention control, blinded or sham CGM and usual care.

11

PICO Scope: Inclusion Criteria• Study design

Focus on high quality (low risk of bias) comparative studies (e.g., randomized controlled trials, crossover trials) for questions 1‐3 as a basis for SoE.

Observational studies (e.g., longitudinal studies correlating intermediate outcomes (e.g., HbA1C) with long term clinical outcomes (e.g. macro or microvascular outcomes, maternal or fetal outcomes);observational studies of safety will be considered;

Formal, full economic studies

• PublicationFull‐length studies published in English in peer‐reviewed journals, FDA reports (EXCLUDED: meeting abstracts, proceedings)

Studies published subsequent to the 2011 report for persons <18 years old and studies published subsequent to the 2012 AHRQ report for adults, those with type 2 diabetes requiring insulin and pregnant women

12


January 19, 2018


Outcomes Primary Clinical Outcomes (SoE)

• Microvascular complications (vision loss, kidney failure, peripheral neuropathy)

• Macrovascular complications (coronary artery, cerebrovascular or peripheral arterial disease)

• Fetal outcomes, cesarean section rates

Primary Intermediate Outcomes (SoE)• Achieving target (age‐appropriate) HbA1c level; “success”, mean (Δ of 0.5% clinically meaningful)

• Maintaining target (age‐appropriate) HbA1c level: “success”, mean• Acute episodes of hypoglycemia (events)

Secondary Intermediate Outcomes• Acute episodes of hyperglycemia• Acute episodes of diabetic ketoacidosis• Quality of life (validated instruments only)

Safety: Morbidity/adverse events from devices, mortality

Economic: ICER, cost savings for prevented morbid event

13

Literature Search Results

*A publication may contribute data to more than one type of diabetes or age group.

14


January 19, 2018


Parallel trial: Patients remain in groups as randomized

Study Participants

Randomization

Treatment A

Treatment B

Treatment A

Treatment B

Cross‐over trial: Patients receive different treatments at different time periods

15

Strength of Evidence (SoE) – Appendices D, EOverall body of evidence for primary outcomes based on:

Risk of bias: the extent to which the included studies protect against bias

Appropriate randomization Allocation concealment Intention to treat analysis Blind assessment of outcomes Co‐interventions applied equally Adequate follow‐up (≥80%), <10% follow‐up difference between groups Control for confounding Additional considerations for cross‐over trials

Consistency: degree to which estimates are similar in terms of range and variability.

Directness: evidence directly related to patient health outcomes.

Precision: level of certainty surrounding the effect estimates.

Publication/report bias: selective reporting or publishing.

16


January 19, 2018


Systematic Review Process

Studies meeting eligibility criteriaEfficacy: RCTs (possibly observational studies)Harms: RCTs, observational studiesEconomic studies

Risk of Bias Appraisal (Study)Low, moderately low, moderately high, high

Synthesis/analysis

Overall Strength of Evidence Determination (GRADE/AHRQ)

17

KQ1: Evidence base for persons with T1DM

5 RCTs (8 pubs.)

8 observational

In previous report: Industry funding?

3 RCTs (4 pubs.) 2 Yes, 1 No

3 observational No

New to report update:

2 RCTs (4 publications) 1 Yes, 1 No

5 observational 2 Yes, 3 No

Persons <18 years old with T1DM

Adults with T1DM

Industry funding?

12 RCTs (15 pubs.) 10 Yes, 2 No

6 observational 2 Yes, 4 No18


January 19, 2018


Persons <18 years old with Type 1 DM

19

KQ1:Persons <18 years old (children, adolescents) with T1DMParallel trials, proportion achieving HbA1c % of <7%

SOE: Low

SOE: Moderate

SOE: Moderate

3 months: More in CGM group achieved success (SOE Low)6, 12 months: No clear difference between CGM and SMBG (SOE Moderate)

20


January 19, 2018


KQ1: Children, adolescents with T1DM: Parallel trials, proportion achieving absolute reduction of ≥ 0.5% for HbA1c

SOE: Low

3 months: More in CGM group achieved success (SOE Low)6 months : No clear difference between CGM and SMBG (SOE Low)

21

KQ1: Children, adolescents with T1DMBetween group difference in mean HbA1c change from baseline

3 months: Small reduction favoring CGM MD‐0.22% (‐0.44% to 0.0%, (SOE Low) 6 months: No clear difference in parallel RCTs; 1 cross‐over trial (N = 72) significant difference during CMG periods: MD ‐0.46%, (‐0.26 %to ‐0.66%) (SOE Moderate)12 months: No difference (SOE Moderate)

22


January 19, 2018


KQ1: Children, adolescents with T1DMTime spent in hypoglycemic range < 70 mg/dL (min/day)

3 months, 6 months : No difference (SOE Low) 23

KQ1: Children, adolescents with T1DMTime spent in hypoglycemic range <55mg/dL (min/day)

3 months, 6 months : No difference (SOE Low) 24


January 19, 2018


KQ1: Children, adolescents with T1DMSevere Hypoglycemic Events

To 12 months: Studies likely underpowered to detect a difference; no difference (SOE Low)

Proportion with ≥1 severe hypoglycemic event

Number of severe hypoglycemic events

25

KQ1: Children, adolescents with T1DM ‐ Severe Hypoglycemic Events

To 12 months: Studies likely underpowered; no difference (SOE Low)

Number of severe hypoglycemic events with seizure, coma or loss of consciousness

Incidence of severe hypoglycemic eventsAuthor, Year(age range)

Follow‐up Incidence: CGM vs. SMBG (p‐value)

Severe hypoglycemic events JDRF 2008 64

(8‐14 years)6 mos events per 100 person years 17.9 vs. 24.4, p=0.64

Bergenstal 2010, STAR 3 15

(children 7‐18 years); ITT w/LOCF12 mos rate per 100 person‐yr, 8.98 vs. 4.95, p=0.35

Kordonouri 2010 70

(1‐16 years) 12 mos P= 0.46

Severe hypoglycemic events with seizure, coma or loss of consciousnessMauras 2012 78 (4 to <10) 6 mos rate per 100 person‐years 8.6 vs. 17.6*

26


January 19, 2018


Children with Type 1 DM: Other Outcomes (SOE not assessed; detail in full report )

• Adherence:

o Single‐arm extensions (case series) generally found that greater CGM adherence/use was associated with better HbA1c levels

o Comparative data: Unclear

• Satisfaction and QOL:

o Sa sfac on: Generally ↑ with CGM vs, SMBG in children, parents; ↑ sa sfac on with ↑ use

o QOL: Generally, no statistical differences (children or parent’s proxy)

27

Adults with Type 1 DM

28


January 19, 2018


KQ1: Adults with T1DMParallel trials, proportion achieving HbA1c % of <7%

SoE Low (all time periods)3 months: More adults achieved success with CGM in individual trials6, months: More adults achieved success with CGM pooled RD: ‐23%, 95%CI ‐36% to ‐10%12 months: More adults achieved success with CGM; RD ‐23%, 95%CI ‐31% to ‐14%)

29

KQ1, Adults with T1DM: Parallel trials proportion achieving specific A1c changes: Low to Moderate Evidence

More achieved success w/CGM 3 months, SoE Low : RD ‐25% (‐50% to 0%)(Beck, significant)6 months, SoE Moderate : RD‐30%, 95% (‐46% to ‐13%)

Relative reduction >10% from baseline in HbA1c

Absolute reduction of ≥ 0.5% from baseline in HbA1c %

More achieved success w/CGM 3 months, SoE Moderate:RD ‐18% (‐28% to ‐8%) 6 months, SoE Low: RD ‐37% (‐54% to 21%)

30


January 19, 2018


KQ1: Adults with T1DM – Parallel trialsBetween group difference in mean HbA1c change from baseline

Traditional GCM (plot) was associated with significant improvement in mean change in HbA1c % from baseline vs. SMBG‐ (SoE Low)

3‐4 months: Pooled MD – 0.43% (‐0.69% to ‐19.0%)6 months: Pooled MD ‐0.52% (‐0.84% to ‐0.19%), 12 months: MD‐0.6% (‐0.76% to ‐0.44%)

Flash CGM vs. SMBG: No difference between groups at 3 or 6 months (1 trial, SOE Insufficient) MD 0% (‐0.17% to 17%) at both times; Baseline A1c 6.79 and 6.78 31

KQ1: Adults with T1DM ‐ difference in mean HbA1c% at last follow‐up: Parallel and cross‐over trials

Traditional GCM was associated with clinically and statistically significant improvement mean HbA1c % at final follow‐up vs. SMBG across parallel trials, statistically significant in cross‐over trials of at least 26 weeks treatment periods (SoE Low) in adults; Findings from 2 trials with newer devices (GOLD and DIAMOND) were similar to those from other trials; 1 showed NS difference (IN CONTROL) 32


January 19, 2018


KQ1: Adults with T1DMTime spent in hypoglycemic range < 70 mg/dL (min/day)

Traditional CGM – Most parallel and cross‐over trials, CGM appears to be associated with decreased time spent in this range vs. SMBG (SOE Low)

Parallel trials (Plot): 3 months (MD ‐21.5 minutes/day (‐36.3 to ‐6.6), 6 months (MD ‐19.7 m/d (‐37.9 to ‐1.5)Cross‐over Trials: 16 week periods, MD ‐1.1 hours/day (‐1.4 to ‐0.8); 26 week periods, MD ‐2.0% (‐2.83% to ‐1.17%) percent of time spent in range

Flash CGM associated with less time in this range (SOE Insufficient): 3 months MD ‐1.09 (±0.18) hours/d, 6 months, MD ‐1.24 (±0.24) hours/d

33

KQ1: Adults with T1DMTime spent in hypoglycemic range < 55 mg/dL

Traditional CGM – Parallel trials‐ minutes/day (SOE Low 3 months, insufficient, 6 months)3 months: decrease in the mean min/d with CGM, MD ‐14.2 minutes/d, (‐23 to ‐5.4) 6 months: No difference, newest trial failed to reach statistical significance

Flash CGM associated with less time in this range (1 trial) (SOE Insufficient): Adjusted MD (SD): 3 months: ‐0.68 ± 0.13 hours/d, 6 months, ‐0.82 ± 0.74 hours/d

34


January 19, 2018


KQ1: Adults with T1DMSevere hypoglycemic events

3 Cross‐over trials: Only one small trial reported statistically fewer events with CGM FCGM: 2% (n =2) of participants in the FCGM and 2% (n=3) in the SMBG group

Proportion with ≥1 severe hypoglycemic event, parallel trials

Number of severe hypoglycemic events, parallel trials

SoE Low Studies were likely underpowered to detect differences between groups; no statistical differences between groups in most trials;

35

Adults with Type 1 DM: Other Outcomes (SOE not assessed; detail in full report)

• Adherence:

o Single arm (case series) extensions of RCTs generally found that greater CGM adherence/use was associated with better HbA1c levels

o Comparative evidence: Unclear


o Sa sfac on: 2 RCTs (1 newer device) ↑ sa sfac on with CGM vs. SMBG; ↑ sa sfac on with ↑ use

o QOL: Results varied across measures

36


January 19, 2018


Mixed Populations(Adults and Children)

with Type 1 DM

• Evidence base:

o 8 RCTs (9 publications); 7 were industry funded

o 2 observational studies; (not industry funded

37

KQ1: Mixed populations (children and adults) with T1DMParallel trials, proportion achieving HbA1c % of <7%

3 months: Significantly more patients in the CGM group achieved target: RD ‐19% (95%CI, ‐32% to 7%)

6 months: No difference between groups

38


January 19, 2018


KQ1: Mixed populations (children and adults) with T1DMBetween‐group differences in HbA1c change from Baseline:

Small reductions favoring CGM (SoE Moderate)3 months: 3 parallel trials (MD ‐0.25%, 95%CI ‐0.48% to ‐0.02%)6 months: 4 parallel trials (MD ‐0.19%, 95%CI ‐0.34% to ‐0.04%);

1 cross over trial, MD ‐0.43, 95%CI ‐0.32 to ‐0.55) N=153Unclear if differences are clinically important

39

KQ1: Mixed population (children, adults) with T1DMTime spent in hypoglycemic range < 70 mg/dL (min/day)

3 months: No difference (SOE Low) 6 months: Less time in range with CGM, Pooled MD: ‐16.26 (‐32.16 to ‐0.37)

40


January 19, 2018


KQ1: Mixed population (children, adults) with T1DMTime spent in hypoglycemic range < 55 mg/dL (min/day)

3 months, 6 months: No difference (SOE Low)

41

KQ1: Mixed population (children, adults) with T1DMSevere Hypoglycemic Events

To 6 months: Studies likely underpowered to detect a difference; No difference (SOE Low);

Proportion with ≥1 severe hypoglycemic event

Number of severe hypoglycemic events

42


January 19, 2018


KQ1: Mixed population (children, adult) with T1DM Severe Hypoglycemic Events

No difference (SOE Low); studies likely underpowered

Number of severe events with seizure, coma or loss of consciousness (parallel trials)

Cross‐over trial: Number and rate of severe hypoglycemic events

Author year Outcome TimingCGM Periods

SMBG Periods

MD (95% CI)Effect Size (SE)

p‐value

SWITCHBattelino 2012Treatment periods: 6 monthsWashout phase: 4 months

Moderately low

Episodes of severe hypoglycemia: requiring assistance, or neurological recovery in response to restoration of plasma glucose to normal)

Across both treatment periods†

4 (5.7 per 100 patient‐years)

2 (2.83 per 100 patient‐years)

NR 0.40

43

Mixed Populations (children and adults) with Type 1 DMOther Outcomes (SOE not assessed; see report)

• Adherence:

o Greater adherence was associated with improved HbA1c

o Comparative: unclear


o Not reported in any included trials or observational studies

44


January 19, 2018


Adults with Type 2 DM

• Evidence base:

o 5 RCTs (7 publications); 4 RCTs were industry funded

o 1 observational study (Industry funded)

45

Outcome

Definition

Studies

Risk of Bias

Reasons for

DowngradingConclusion Quality

Success (Achieving

HbA1c %

<7.0%)

1 RCT(Beck

2017[b])

N = 152

Moderately

Low RoB

3, 6 mos.

Imprecision (‐1) 3 months: CGM 22%, SMBG 12%Adjusted RD: 10%, 95% CI −2% to 23%6 months: CGM 11%, SMBG 9%Adjusted RD: 3%, 95% CI −9% to 14%

Conclusion: No clear difference at 3 months; no difference at 6 months.

⨁⨁◯◯

LOW

HbA1c%: Absolute

reduction of

≥0.5% from

baseline

Absolute reduction3 months: CGM 61%, SMBG 38%Adjusted RD: 31%, 95% CI 5% to 57%6 months: CGM 56%, SMBG 37%Adjusted RD: 26%, 95% CI 0% to 50%

Conclusion: More CGM patients achieved ≥0.5% reduction in HbA1c at both time points.

⨁⨁◯◯

LOW

KQ1: Adults with T2DM

46


January 19, 2018


KQ1: Adults with T2DMBetween‐group differences in HbA1c change from baseline

3 months: Clinically and statistically sig. reduction with CGM 6 months: Statistically sig. reduction with CGM9, 12 months: No difference (1 small trial)FCGM: adjusted MD at 6 months: 0.03 (SE 0.114), p=0.822 (SOE Insufficient)

SOE Moderate

SOE Low

SOE Insuff. (9, 12 mos.)

47

Hypoglycemia <50 mg/dL

• 3 months (2 RCTs, N=242)

• 6 months (1 RCT, N=146)

SOE Low for both time points

Hypoglycemia <70 mg/dL

• 3 months (2 RCTs, N=242)



SOE Low for 3 and 6 mos., Insufficient for 12 mos.

KQ1: Adults with T2DMHypoglycemia, range <50 and < 70 mg/dl

No differences between CGM and SMBG in minutes per day, % of readings per day, or % of time spent in either range:

FCGM (1 RCT, N=224): <55 mg/dl

6 months MD ‐13. 2 min/d favoring FCGM vs. SMBG SOE Insufficient FCGM (1 RCT, N=224): <70 mg/dl

6 months MD ‐28.8 min/d favoring FCGM vs. SMBG SOE Insufficient

48


January 19, 2018


OutcomeStudies

RoB

Reasons for

DowngradingConclusion Quality

Episodes of Severe

Hypoglycemia

3 RCTs

N=264

(Beck

2017[b],

Tildesley

2013, Yoo

2008)

3‐6 mos

Imprecision

(‐2)No episodes (defined as requiring

third party assistance) in one trial

over 6 months

Two trials did not define severe hypoglycemia: one reported no events over 3 months; second reported frequency in both CGM and SMBG group was “negligible with no serious events” (data NR, 6 months).

Conclusions: Trials underpowered;

no differences between groups.

⨁⨁◯◯

LOW

KQ1: Adults with T2DMEpisodes of Severe Hypoglycemia

Flash CGM (N=224, Haak 2016): No difference, study underpowered, SOE Insufficient: FCGM, 3 patients (2%) vs. SMBG, 1 patient (1%) (event requiring third party assistance).

49

Adults with Type 2 DMOther Outcomes (SOE not assessed, see report)

• Adherence: Greater sensor use associated with greater reduction in HBA1c % to 12 months (1 RCT)

• Comparative data unclear


o Satisfaction: CGM usage associated improved satisfaction in trials of traditional CGM and flash CGM.

o QOL: NS differences in any measure for TCGM (1 trial in newer device, 1 trial in older device) or in most measures for FCGM (1 trial)

50


January 19, 2018


Diabetes in Pregnancy

Pre‐existing Type 1 DM

o 2 RCTS (industry funded)

o 3 observational (1 industry funded, 1 not, 1 unclear)

Pre‐existing Type 2 DM

o 1 RCT (industry funded)

Gestational Diabetes

o 1 RCT (funding unclear)

51

Statistically significant, clinically important difference favoring CGM for the following outcomes (wide CIs):

• Caesarean section (2 RCTs, N=325), SOE Moderate:

CGM 50.9%, SMBG 62.3%

Pooled RD: ‐11.0%, 95% CI ‐21.0% to ‐1.0%, I2 = 0%

• Admission to NICU, >24 hours (1 RCT, N=200), SOE Low:

CGM 27%, SMBG 43%

RD ‐16%, 95% CI ‐29% to ‐3%

Satisfaction: favorable ratings with CGM; NS difference in QOL measures

KQ1: Pregnancy, Preexisting T1DM

52


January 19, 2018


KQ1: Pregnancy, Preexisting T1DM, cont.

No statistically significant difference (studies may have lacked power for some outcomes) between CGM and SMBG for the following outcomes:

SOE Moderate (2 RCTs):• Gestational age; Birthweight; Miscarriage; Preterm Delivery;

Preeclampsia (SOE Moderate, RCTs)SOE Low (1 to 2 RCTs):• Large for gestational age; Episodes of severe neonatal and

severe maternal hypoglycemia; Hypoglycemia (neonatal, maternal); Still birth; Birth trauma; and HbA1c% measures (success, ≤6.5%; mean change from baseline)

SOE Insufficient (1 to 2 RCTs):• Major congenital anomalies; Time spent in hypoglycemia

(≤70 or <63 mg/dl range)

53

KQ1: Pregnancy, Preexisting T2DM

No difference between CGM and SMBG in any outcome measured in one small trial (N=31) due at least in part to small sample size; all evidence considered. Insufficient SOE:

• Gestational age• Birth weight• Large for gestational age• Neonatal hypoglycemia• Miscarriage• Perinatal mortality• Caesarean section• HbA1c%• Hypoglycemia (% of SMBG values ≤70 mg/dl)• Severe Hypoglycemia (episodes requiring 3rd party help)

54


January 19, 2018


KQ1: Gestational Diabetes

No difference between CGM and SMBG in any outcome measured in one trial (N=106); Study was likely underpowered to detect most outcomes; all evidence considered Insufficient:

• Gestational age• Birth weight• Large for gestational age• Macrosomia• Neonatal hypoglycemia• Perinatal mortality• Caesarean section• HbA1c% (mean change from baseline)

55

KQ2: Safety and Harms: AEs leading to discontinuationOutcome, f/u

Studies Downgrade Conclusion Quality

Adverse events leading to discontinuation3‐6.5 months

Traditional CGM8 RCTs (N=25 to 142)

2 observational (N=83 to 1714)

Inconsistent ‐1Imprecise ‐1

Frequency (RCTs): 0% to 24%. Older devices, from 2% to 24%; most common Difficulty operating device and/or sensor (3% to 8%, 3 RCTs)

Alarms too frequent (6% , 2 RCTs) Discomfort or inconvenience; (20%, 1 small RCT, n=25)

Newer devices (2 trials, N=52, 142): Allergic reaction to sensor (1%) Could not upload CGM data (4%)

Observational studies: 61%, 44%, similar reasons

Conclusion: Discontinuation not uncommon; most were due to difficulty operating the device or bothersome alarms

⨁⨁◯◯LOW

Flash CGM2 (N=269)6 months

Risk of bias ‐1

Inconsistent ‐1

Imprecise ‐1

Frequency 2% to 5% included: itching, rash, erythema, weeping at insertion site; severity of events unclear/not defined. Conclusion: Site‐related AE discontinuation was not common;

⨁◯◯◯

INSUFFICIENT

56


January 19, 2018


KQ2: Serious device‐related AE (proportion with ≥ 1 event)Outcome, f/u


Serious device related adverse events (proportion with ≥1 event)

6‐12 monthsTCGM: 11 RCT (N=14 to 244)

Inconsistent ‐1

Imprecise ‐2Frequency (all RCTs) 0% to 7%, Excluding very small trial (n=14), frequency 0%‐3%.Older devices (9 RCT): 0% to 7%, included: Hospitalization for DKA (2% to 7%, 2 trials); 2% (1/44) caused by pump failure.

Serious skin reactions (0% to 6%, 2 trials) Diabetes‐related hospitalization (3%, 1 trial) Insertion site infections resulting in cellulitis, skin abscess (1% each, 3 trials)

Serious device or study related AE not otherwise specified (0%, 2 trials)

Newer (2 RCT, N=52 ,142): 0% ‐ 1%; Retinal detachment (1%)

Conclusion: Serious device‐related AE (as reported by authors) were relatively rare. Sample size may be too small to detect

⨁⨁◯◯

LOW

Flash CGM2 (N=269)

Risk of bias ‐1

Inconsistent ‐1

Imprecise ‐1

Frequency, 1% to 3%: Sensor site allergic, reaction necrosis or infection; rash, erythema, pain, itching

Conclusion: AEs appear to be rare; severity not defined

⨁◯◯◯

INSUFFICIENT

57

KQ2: Technical or mechanical issues

Outcome, f/u


Technical or

mechanical

issues

3 months

4 (N=27 to 157)

Risk of bias ‐1

Imprecise ‐1Frequency (3 RCTs) 1% to 16%

Sensor‐related, loss of all glucose readings (15%) Mechanical problems, not further specified (16%)

“Device issue” (1%) (newer CGM device; Lind)

Women with preexisting T1DM during pregnancy ( 1 RCT, n=103 CGM), older CGM device (Feig):

81% reported issues related to transmitter/receiver connection, various sensor problems; others (not specified)

78% did not use the device (alarms too frequent, inaccurate readings, too difficult to operate, sensor errors, calibration issues, other)

Conclusion: Definitions and reporting of technical or mechanical issues varied and were not well reported across trials

⨁⨁◯◯

LOW

58


January 19, 2018


KQ2: Non serious device‐related AE (proportion with ≥1 event)

Non serious device‐related adverse events (proportion with ≥1 event)3 to 8.5 months

7 RCT (N=25 to 157)

1 prospective cohort (n=83)

Risk of bias ‐1Imprecise ‐1

Frequency 0% to 45% (RCTs). Sensor or insulin infusion site skin‐related AE accounted for most (e.g., erythema, inflammation, rash/allergic reaction, mild infection) Excluding trial of preexisting type 1 DM during pregnancy which reported 45% with skin change range was 0% to 24%.

Newer device (N= 142, Lind): 3% skin‐related problems, including allergic reaction to sensor, inflammation, itching, and rash at application site.

Cohort study local skin reaction/irritation(36%)

Conclusion: Non‐serious device related adverse events, especially skin‐related problems, are common

⨁⨁◯◯LOW

Flash CGM2 (N=269)

Risk of bias ‐1Inconsistent ‐1Imprecise ‐1

Frequency 4% to 8%; allergic reaction at sensor site, rash, erythema, pain, itching, edema, site infection

Also reported “expected sensor‐insertion site symptoms” (not considered AEs by the authors) in up to 40% of subjects; Events similar to those reported as “non‐serious device‐related”; unclear how outcomes differ and if there is overlap between them.

Conclusion: Definitions of adverse events/distinction between events and symptoms was unclear.

⨁◯◯◯INSUFFICIENT

59

KQ3: Differential Efficacy and Harms

RCTs

Exposure

Outcome

(F/U)Downgrade Conclusion Quality

T1DM1 RCT N = 155(Beck 2017[a])T2DM1 RCT N = 152(Beck 2017[b])

ExposuresBaseline HbA1c;Age;Percent CGM time <70 mg/dL; SMBG frequency;Education;Hypoglycemia Unawareness Score;Diabetes Numeracy Score;Hypoglycemia Fear Total Score; Clinical site (T1DM only)

Δ baseline

HbA1c %

6 months

Consistency

(Unknown)

Indirect (‐1)

Imprecise (‐1)

HTE (‐1)

T1DM

No factors modified effect.

T2DM

Baseline Hypoglycemia Unawareness Survey scores: greater ↓ in mean HbA1c % levels in subjects with reduced awareness or uncertainty (score ≥3), vs. higher awareness (score ≤2), following CGM but not SMBG (interaction p=0.031).

No other factors modified

Conclusion: Insufficient evidence precludes drawing firm conclusions.

⨁◯◯◯

INSUFFICIENT

60


January 19, 2018


KQ 4: Full Economic Studies – Adults T1DM, non U.S. Studies Chaugule 2017

Canada QHES 86/100

Roze 2014

Sweden QHES 93/100

Population

AdultsMean 46 y.o., 53% Male

Baseline HbA1c = 8.6%

MDI

Mean 27 y .o., 54.5% Female

Baseline A1c = 8.6%

Assumed 13 yrs. since diagnosis, CSII

Clinical data DIAMOND Trial IMS CORE Diabetes Model, DCCT, pubs

Time horizon 50 years 70 years

ICER $43,926/QALY $57,433 / QALY

SA Range $42,552 to $84,972 $43,751 to $92,759

Author’s

ConclusionAt WTP threshold of $50,000 CGM robustly,

cost effective vs. SMBG

CGM is a cost–effective option in the

treatment of T1DM in Sweden

Limitations Canadian societal perspective stated; only

direct costs reported

SA for long‐term micro‐ and macrovascular

complications not presented

Lifetime horizon; RCT data to 12 months.

Change in HbA1C based on DIAMOND

trial; Unclear if 1% change over lifetime

sustainable.

Industry funded

Swedish societal perspective

Limited acknowledgment of modeling,

study limitations

Lifetime horizon; RCT data provide

information up to 12 months.

Industry funded

61

KQ 4: Full Economic Studies – Adults T1DM, U.S. Studies

Huang 2010

U.S. QHES 85/100

McQueen 2011

U.S. QUES 93/100

Population

Adults

Two A1c cohorts :

Mean 43 y.o. (25‐73) 57% Female;

Baseline A1c = 7.6 (SMBG), 7.1% (CGM):

A1c <7.0% (age 31y.o., 8‐65); MDI and CSII

Mean 40 y.o.

Baseline HbA1c = 7.6%

20 yrs. since diagnosis

MDI and CSII

Clinical JDRF, DCCT, pubs C.D.C. CE group; experts, DCCT, pubs

horizon Lifetime 33 years

ICER $98,679 /QALY $45,033 / QALY

SA Range $70,000 to $701,397 $12, 000 to $300,000; CE in 48% Monte Carlo

simulations at < $50,000; 70% of simulations

< $100,000/QALY

Author’s

ConclusionWide CI (CGM dominating, being dominated

by SMBG); Immediate QOL of CGM

responsible majority of projected lifetime

benefits

CGM cost effective in more circumstances

than not at WTP of $100,000.

Limitations CV complications From T2DM CV model

Lifetime horizon (RCT data to 12 months)

High baseline utilities ‐ ceiling on potential

OQL benefit of CGM

Unclear if models for microvascular and CV

complications reflect current care

JDRF grant

Some costs were extrapolated from

studies that include all age groups.

Time horizon; sustainability of improved

A1C unclear

Substantial variation in ICER based on

SA/modeling of complications based on

probabilities from different populations62


January 19, 2018


KQ 4: Full Economic Studies – Adults T2DM, non U.S. Studies Type 2 Studies: Fonda 201637 U.S. QHES 75/100

Population

Adults

57.8 y.o.; T2DM least 3 months.

Not taking prandial insulin. Initial A1C of between 7% and 12% ; MDI and CSII

Perspective Third‐party payer (direct costs only)

Time horizon Lifetime

Clinical data Risk adjustments from UKPDS, DCCT Framingham Heart Study, literature, CORE

Diabetes Model

ICER $8,898 / QALY

SA Probabilistic cost‐effectiveness analysis: likelihood CGM CE 70% at the

willingness‐to‐pay threshold of $100,000/QALY.

Author’s

Conclusion

CGM offers a cost‐effective alternative to populations matching that the trial

specifically: short‐term, intermittent use in people with type 2 diabetes.

Limitations Small sample size of trial (n = 100) to estimate effectiveness parameters.

Limited sensitivity analyses presented; results of one‐way SA not discussed

Used older CGM device that has since been update.

Life‐time horizon used; Few RCT data on long‐term CGM use in type 2 DM.

Unclear if DCCT, USPKD, Framingham complications data reflect current care

Industry funding (Dexcom Grant)

63

Summary: KQ1, Efficacy in Children with T1DM

Outcome 3 months 6 months 12 months

Success

(HbA1c% <7%)

Effect RD ‐19% (‐32% to ‐5%)

1 RCT

NS

2 RCTs

NS

1 RCT

SoE ⨁⨁ ⨁⨁⨁ ⨁⨁⨁

Mean

HbA1C%

change

Effect MD ‐0.22% (‐44% to 0.0%)*

3 RCTs

NS

4 Parallel RCTs

NS

2 RCTs (heterog)

SoE ⨁⨁ ⨁⨁⨁ ⨁⨁⨁

Hypoglycemia

(Time at <70

or <55mg/dL)

Effect NS

2 RCTs

NS

2 RCTs

NS

1 RCT

SoE ⨁⨁ ⨁⨁ ⨁⨁

Severe

Hypoglycemic

Events

Effect ↓ power, NS ↓ power, NS ↓ power, NS

SoE ⨁⨁ ⨁⨁ ⨁⨁

Favors CGMModerate

Favors CGMLow

NS differenceModerate

NS differenceLow

INSUFFICIENT

*MS=marginally significant, clinical significance unclear; 6 months 1 cross‐over trial MD ‐0.46% favored CGM

64


January 19, 2018


Summary: KQ1, Efficacy in Adults with T1DM: HbA1c%

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

Parallel Trials

Outcome 3 months 6 months 12 months

Success

(HbA1c% <7%)

(TCGM)

ES 1RCT RD ‐10% (‐18% to ‐1%)*

1RCT RD ‐29% (‐46% to ‐13%)

Heterogeneous

RD ‐23% (‐36% to ‐10%)

3 RCTs

RD ‐23% (‐31% to ‐14%)

1 RCT

SoE⨁⨁ ⨁⨁ ⨁⨁

Mean

HbA1C%

change

(TCGM)

ESMD ‐0.43 (‐69 , ‐19)

6 RCTs (Heterogeneous)

MD ‐0.52 (‐0.84, ‐0.19)

4 RCTs (Heterogeneous)

MD ‐0.60 (‐0.76, 0.44)

(1 RCT)

SoE⨁⨁ ⨁⨁ ⨁⨁

Mean A1C %

change

(FCGM, 1 RCT)

ES NS NS NR

SoE INSUFF INSUFF NR

TCGM Difference in final mean A1C % (SOE LOW)

6 Parallel RCTs (3‐12 months) Pooled MD ‐0.48 (‐0.7 to ‐0.28)

2 Cross‐over (26 weeks) Pooled MD ‐0.42 (‐0.51 to ‐0.33)

2 Cross‐over (4‐16 weeks) NS

Cross‐over Trials

65

Summary: KQ1, Efficacy, adults with T1DM: Hypoglycemia

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

*Includes parallel and cross‐over trials

Outcome 3‐4 months* 6 months*

Hypoglycemia

(↓ Time at <70

mg/dL)

TCGM

ES MD ‐21m/d (‐36.3, ‐6.6) 2 PRCT

MD ‐66 m/d (‐84m, ‐48) 1 CRCT

MD ‐19.7 m/d (‐37.9, ‐1.5) 2 PRCT

MD ‐2.0% time (‐2.8, ‐ 1.2) 1 CRCT

SoE⨁⨁ ⨁⨁

Hypoglycemia

(↓ Time <70 mg/dL)

Flash CGM (1 trial)

ES MD ‐65.4 m/d MD ‐74.4 m/d

SoE INSUFF INSUFF

Hypoglycemia

(↓ Time <55mg/dL)

TCGM

ESMD ‐14 m/d (‐23 to ‐5.4)

2 trials

MD ‐22m/d(‐30.4, ‐13,63) 1 PRCT

MD ‐4.3m/d (‐11.7, 3.0) 1 PRCT

(Heterogeneous)

SoE ⨁⨁ INSUFF

Hypoglycemia

(↓ Time at <55mg/dL)

Flash CGM (1trial)

ESMD ‐ 40.8 m/day MD ‐49.2 m/d

SoE INSUFF INSUFF

Severe Hypoglycemic

Events

ES ↓ power, NS ↓ power, NS

SoE ⨁⨁ ⨁⨁

66


January 19, 2018


Summary: Efficacy, mixed populations (children, adults) with T1DM:

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

*clinical significance unclear

Outcome 3 months 6 months

Success

(HbA1c% <7%)

ES RD‐19% (‐32%, ‐7%)

3 RCTs

NS

2 RCTs

SoE ⨁⨁ ⨁⨁

Mean A1C%

change

ES MD ‐0.25%* (‐0.48%, ‐0.02%)

3 RCTs

MD ‐0.19% (‐0.34%, ‐0.04%) 4 PRCTs*

MD ‐0.43 (‐0.32%, ‐0.55%) 1 CRCT

SoE ⨁⨁⨁ ⨁⨁⨁

Hypoglycemia

(↓Time at <70

mg/dL)

ES NS

2 RCTs

MD ‐16.3 m/d (‐32.2, ‐0.37)

4 RCTs

SoE ⨁⨁ ⨁⨁

Hypoglycemia

(↓Time at

<55mg/dL)

ES NS

2 RCTs

NS

3RCTs

SoE ⨁⨁ ⨁⨁

Severe

Hypoglycemic

Events

ES ↓ power, NS, 4 RCTs ↓ power, NS, 6 RCTs

SoE ⨁⨁ ⨁⨁

67

Summary: KQ1, Adults with T2DM, HbA1c % outcomes

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

Outcome 3 months 6 months 9, 12 months

Success

(HbA1c% <7%)

ESadj. RD 10% (‐2% , 23%)

(1 trial)

adj. RD 3% (‐9%, 14%

(1 trial)NR

SoE ⨁⨁ ⨁⨁

HbA1c%

absolute

reduction

≥0.5%

ES adj. RD 31%

(1 trial)

adj. RD 31%

(1 trial)NR

SoE ⨁⨁ ⨁⨁

Mean

HbA1C%

change

TCGM

ESMD ‐0.49% (‐0.71, ‐0.2)

(3 trials)

MD ‐0.37% (‐0.59, ‐0.14)

(3 trials)9 mos (NS)

12 mos (NS)

1 trialSoE ⨁⨁⨁ ⨁⨁⨁

Mean HbA1C%

change, FCGM

ES NR NS, 1 trial NR

SoE INSUFF

68


January 19, 2018


KQ1 Summary: Adults with T2DM, Hypoglycemia Outcomes

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

Outcome 3 months 6 months

<50 mg/dl: min/day,

% of readings, or %

time

TCGM

ES NS

2 RCT

NS

1 RCT

SoE ⨁⨁ ⨁⨁

<55 mg/dl: minutes/

day

FCGM (1 trial)

ES NR Adj. MD ‐13.2 min/d (SE 4.1)

SoE INSUFF

<70 mg/dl: min/day,

% readings day, or %

time, TCGM

ES NS

2 RCT

NS

1 RCT

SoE ⨁⨁ ⨁⨁

<70 mg/dl: min/day

FCGM (1 trial)ES NR Adj. MD ‐28.2 minutes (SE 8.0)

SoE INSUFF

Episodes, severe

hypoglycemia, TCGMES ↓ power, NS (3 RCTs) ↓ power, NS (3 RCTs)

SoE ⨁⨁ ⨁⨁

Episodes, severe

hypoglycemia, FCGMES ↓ power, NS, ↓ power, NS

SoE INSUFF INSUFF

69

KQ 2 Summary: Safety

Moderate Low INSUFFICIENT

Inconsistent definitions, classification, reporting of AEs make conclusions challenging. There are limited data on newer devices. Most AEs relate to sensor‐related skin problems. AEs for CGM only

Outcome AEs leading to discontinuationTCGM

Effect Older devices (8 RCT): Operation (3%), alarm frequency (6%), discomfort, inconvenient (5/25pts)Newer (2 RCT): Allergic rx (1% ), cannot upload data (4%)2 Observational studies 44%, 61%

SoE ⨁⨁AEs leading to discontinuationFlash CGM

Effect 2% to 5%: itching, rash, erythema, weeping at insertion site; severity of events unclear/not defined.

SoE Insufficient

Serious device related AE (≥1 AE)TCGM

EffectOlder (9 RCT): Hospitalization (DKA 2%‐7%, other (3%); Skin reaction (0‐6%), infection (leading to cellulitis, abscess 1%)Newer (2 RCT): 0% ‐ 1%; Retinal detachment (1%)

SoE ⨁⨁

Serious device related AE (≥1 AE)Flash CGM

Effect1‐3% Site allergic reaction, necrosis, infection, rash, erythema, pain, itching

SoE Insufficient

70


January 19, 2018


KQ 2 Summary: Safety

Inconsistent classification, reporting of AEs make conclusions challenging; limited data on newer devices

Moderate Low INSUFFICIENT

Outcome

Technical, mechanical issues (3 months)

Effect 4 RCTs: 1% (not defined, new device) to 16% (sensor issues w/data loss, mechanical problems)

1 RCT: T1DM in pregnancy: 81% (transmitter/receiver connection, sensor problems); 78% didn’t use (alarm frequency, sensor or reading errors, calibration, difficulty operating)

SoE ⨁⨁Non‐serious AE (≥1 AE)TCGM

Effect 0% to 45% (7 RCTs), Excluding RCT of T1DM in pregnancy range was 0% to 24%. Sensor or insulin infusion site skin‐related AE accounted for most

Newer device (1RCT: 3% skin‐related problems); Cohort study: 36% (local skin reaction/irritation)

SoE ⨁⨁

Non‐serious AE (≥1 AE)Flash CGM

Effect 4% to 8%; allergic reaction, infection at sensor site, rash, erythema, pain, itching, edema; reported “expected sensor‐insertion site symptoms” (not considered AEs by the authors) in up to 40% of subjects; distinction between events and symptoms was unclear

SoE Insufficient

71

Summary: KQ1, Preexisting T1DM in PregnancyOutcome Up to 36 gest. weeks

Caesarean section ES RD ‐11% (‐21%, ‐1%), 2 trials

SoE ⨁⨁⨁

Admission to NICU ES RD ‐16% (‐29%, ‐3%) 1 trial

SoE ⨁⨁

Gestational age; Birthweight; Miscarriage;

Preterm Delivery; Preeclampsia; Studies may be

underpowered to detect some outcomes

ES NS (2 trials)

SoE ⨁⨁⨁

Large for gestational age; episodes of severe neonatal and severe maternal hypoglycemia; Hypoglycemia (neonatal, maternal); Still birth; Birth trauma; and HbA1c% measures (success, ≤6.5%; mean change from baseline); Studies may be underpowered to detect some outcomes

ES NS (1‐2 trials)

SoE ⨁⨁

Major congenital anomalies; Time spent in hypoglycemia (≤70 or <63 mg/dl range)

ES NS (1‐2 trials)

SoE ⨁

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

72


January 19, 2018


Summary: KQ1, Preexisting T2DM in PregnancyOutcome Up to 36 gest. weeks

Gestational age; Birth weight; Large for gestational

age; Neonatal hypoglycemia; Miscarriage; Perinatal

mortality; Caesarean section; HbA1c%; Hypoglycemia

(% of SMBG values ≤70 mg/dl); Severe Hypoglycemia

(episodes requiring 3rd party help); low power

Effect NS (1 small trial)

SoE ⨁

Favors CGMModerate

Favors CGMLow


NS differenceLow

INSUFFICIENT

Outcome Up to 36 gest. weeks

Gestational age; Birth weight; Large for

gestational age; Macrosomia; Neonatal

hypoglycemia; Perinatal mortality; Caesarean

section; HbA1c% (mean change from baseline);

low power

Effect NS (1 trial)

SoE ⨁

Summary: KQ1, Gestational Diabetes

73

Summary: Full economic studies

Cost‐effectiveness:

• Adults with T1DM (4 studies): CGM may be cost‐effective at WTP $100,000/QALY; ICERs ranged from $43,926/QALY to $98,679 /QALY; wide range of ICERs from sensitivity analyses; long time horizon

• Adults with T2DM (1 study): CGM may be cost‐effective 70% at WTP $100,000/QALY. Long time horizon

• No Evidence: Children/adolescents, patients with pre‐existing DM in pregnancy, those with GDM or those >65 years old or FCGM

74


January 19, 2018


Considerations and remaining questions

• Baseline HbA1c% for most studies of TCGM in T1DM was ≥ 8%; only trial of FCGM in T1DM baseline A1c was <7%

• Impact of CGM data and how it is used in daily decision making is unclear

• Which patients may benefit most from CGM is unclear

• Daily sensor use/adherence in trials vs. real world

• Trial data to 12 months; efficacy and safety of daily use for longer periods of time is unclear

• Few studies with newer devices, none in children; some results across newer and older devices are similar

• Use in >65 years olds not described in comparative studies of traditional CGM

• No long term data on macro or microvascular disease

75

Continuous glucose monitoring: Final key questions Page 1 of 3

FINAL key questions and background

Continuous glucose monitoring

Background

Diabetes mellitus (DM), or diabetes, is a serious metabolic disease characterized by chronic elevation of blood glucose (i.e., hyperglycemia) resulting from defects in insulin secretion, insulin action, or both. No definitive cure is known at this time. Diabetes is generally categorized into three major types based on etiology: Type 1 diabetes (T1DM) (formerly called juvenile diabetes or insulin-dependent diabetes mellitus [IDDM]), Type 2 diabetes (T2DM) (formerly called adult onset diabetes mellitus [AODM] or non-insulin dependent diabetes [NIDDM]), and gestational diabetes mellitus (GDM). Diabetes is a leading cause of morbidity and mortality and is associated with substantial healthcare and societal costs. An estimated 29.9 million Americans (9.3% of the population) had diabetes in 2015 and, by 2050, the prevalence of diabetes in the U.S. adult population is projected to increase to between 21% and 33%. Serious complications related to diabetes include diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome (HHNS), as well as longer term morbidity due to microvascular (e.g., retinopathy, nephropathy, neuropathy) and macrovascular (e.g., heart disease, stroke) complications; other diabetes related complications include increased risk of infections, cancer and other autoimmune disorders including celiac sprue, thyroid disease, rheumatoid arthritis, and vitiligo. Intensive insulin therapy, a term used to describe tight management of blood glucose levels, has been shown to reduce the risk of long-term diabetic complications by lowering average blood sugar levels, but also increases the risk of hypoglycemia, which can result in serious morbidity and even death, and causes fear of hypoglycemia which is a major barrier to optimal glucose control. Real-time continuous glucose monitoring (CGM) is advanced glucose monitoring technology that continuously measures interstitial glucose levels, displays the current blood glucose level as well as the direction and rate of change, and uses alarms and alerts to inform patients when blood glucose is exceeding or falling below specified thresholds. Conventional fingerstick self-monitoring of blood glucose (SMBG), sometimes called intermittent monitoring, is a technique for testing blood glucose using a portable glucose meter designed for home use. SMBG provides an instantaneous reading of current blood glucose levels at single points in time, but cannot indicate whether the glucose level is on its way up or down. CGMs were designed to aid in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long term therapy adjustments, which may minimize these excursions. With the exception of one FDA-approved device (Dexcom G5 Mobile CGM System), CGMs are intended to complement, not replace, information obtained from a standard home glucose monitoring device; they are not intended to be used directly for making therapy adjustments, but rather to provide an indication of when a fingerstick may be required. CGMs can be used as stand-alone devices or in conjunction with compatible insulin pumps.

Policy context

This topic was originally reviewed in 2011. It is proposed for re-review based on new evidence and newly expanded indications for continuous glucose monitoring (CGM). New evidence and indications are identified that support re-reviewing the evidence for continuous glucose monitoring.

WA – Health Technology Assessment September 11, 2017


Objectives

The first aim of this report is to update the 2011 HTA on glucose monitoring in children and adolescents by systematically reviewing, critically appraising and analyzing new research evidence on the safety and efficacy of continuous glucose monitoring in persons under 18 years old with insulin requiring diabetes mellitus. The second aim is to systematically review, critically appraise and analyze research evidence on the safety and efficacy continuous glucose monitoring in persons with type 1 or type 2 diabetes (regardless of insulin requirement), including pregnant women with pre-existing or gestational diabetes. SMBG as a stand-alone means of monitoring blood glucose will not be included as an intervention.

Key questions

In persons with diabetes mellitus (DM):



3. What is the evidence that glucose monitoring has differential efficacy or safety issues in sub-populations?

4. What is the evidence of cost-effectiveness of continuous glucose monitoring?

Scope

Population: Persons with diabetes mellitus, including those with type 1 and type 2, and pregnant women with pre-existing diabetes or gestational diabetes

Interventions: FDA-approved real-time continuous glucose monitoring devices and FDA-approved combination devices integrating real-time continuous glucose monitoring with insulin pump/infusion (including sensor augmented insulin pumps).

Comparators: Self-monitoring using convention blood glucose meters, attention control, blinded/sham CGM, and usual care.

Outcomes:

Primary clinical outcomes:

Microvascular complications (e.g., vision loss, kidney failure, peripheral neuropathy, objectively assessed)

Macrovascular complications (e.g., coronary artery, cerebrovascular or peripheral arterial disease, objectively assessed)

Fetal outcomes, cesarean section rates

Primary intermediate outcomes:

Achieving target (i.e. age-appropriate) HgA1C level

Maintaining target (i.e. age-appropriate) HgA1C level

Acute episodes of hypoglycemia

Secondary intermediate outcomes

Acute episodes of hyperglycemia

Acute episodes of diabetic ketoacidosis

Quality of life (validated instruments only)

WA – Health Technology Assessment September 11, 2017


Safety outcomes:

Mortality

Morbidity from glucose meters or monitors

Economic outcomes:

Long term and short term comparative cost-effectiveness measures

Studies:

Only high quality (low risk of bias) comparative studies will be considered for Key Questions 1-3. Observational studies with longer term clinical outcomes or safety outcomes will be considered for Key Questions 1 and 3. Full, formal economic studies (i.e., cost-effectiveness, cost-utility, cost-minimization, and cost-benefit studies) will be sought for Key Question 4; studies using modeling may be used to determine cost-effectiveness over the full duration of glucose monitoring, which is a lifetime. Observational studies of safety will be considered.

Analytic framework

*Fetal outcomes include gestational age, birth weight, frequency of neonatal hypoglycemia, birth trauma, major and minor anomalies, admission to a neonatal intensive care unit, stillbirth, and neonatal and perinatal mortality.

Public comment and Response

See Draft key questions: Public comment and response document published separately.

1

HTCC Coverage and Reimbursement Determination Analytic Tool

HTA’s goal is to achieve better health care outcomes for enrollees and beneficiaries of state programs by paying for proven health technologies that work.

To find best outcomes and value for the state and the patient, the HTA program focuses on three questions:

1. Is it safe? 2. Is it effective? 3. Does it provide value (improve health outcome)?

The principles HTCC uses to review evidence and make determinations are:

Principle One: Determinations are evidence-based HTCC requires scientific evidence that a health technology is safe, effective and cost-effective1 as expressed by the following standards2:

Persons will experience better health outcomes than if the health technology was not covered and that the benefits outweigh the harms.

The HTCC emphasizes evidence that directly links the technology with health outcomes. Indirect evidence may be sufficient if it supports the principal links in the analytic framework.

Although the HTCC acknowledges that subjective judgments do enter into the evaluation of evidence and the weighing of benefits and harms, its recommendations are not based largely on opinion.

The HTCC is explicit about the scientific evidence relied upon for its determinations.

Principle Two: Determinations result in health benefit

The outcomes critical to HTCC in making coverage and reimbursement determinations are health benefits and harms3:

In considering potential benefits, the HTCC focuses on absolute reductions in the risk of outcomes that people can feel or care about.

In considering potential harms, the HTCC examines harms of all types, including physical, psychological, and non-medical harms that may occur sooner or later as a result of the use of the technology.

Where possible, the HTCC considers the feasibility of future widespread implementation of the technology in making recommendations.

The HTCC generally takes a population perspective in weighing the magnitude of benefits against the magnitude of harms. In some situations, it may make a determination for a technology with a large potential benefit for a small proportion of the population.

In assessing net benefits, the HTCC subjectively estimates the indicated population's value for each benefit and harm. When the HTCC judges that the balance of benefits and harms is likely to vary substantially within the population, coverage or reimbursement determinations may be more selective based on the variation.

1 Based on Legislative mandate: See RCW 70.14.100(2). 2 The principles and standards are based on USPSTF Principles at: Hhttp://www.ahrq.gov/clinic/ajpmsuppl/harris3.htm 3 The principles and standards are based on USPSTF Principles at: Hhttp://www.ahrq.gov/clinic/ajpmsuppl/harris3.htm

http://www.ahrq.gov/clinic/ajpmsuppl/harris3.htm

http://www.ahrq.gov/clinic/ajpmsuppl/harris3.htm

2

The HTCC considers the economic costs of the health technology in making determinations, but costs are the lowest priority.

Using evidence as the basis for a coverage decision Arrive at the coverage decision by identifying for Safety, Effectiveness, and Cost whether (1) evidence is available, (2) the confidence in the evidence, and (3) applicability to decision. 1. Availability of Evidence:

Committee members identify the factors, often referred to as outcomes of interest, that are at issue around safety, effectiveness, and cost. Those deemed key factors are ones that impact the question of whether the particular technology improves health outcomes. Committee members then identify whether and what evidence is available related to each of the key factors.

2. Sufficiency of the Evidence:

Committee members discuss and assess the evidence available and its relevance to the key factors by discussion of the type, quality, and relevance of the evidence4 using characteristics such as:

Type of evidence as reported in the technology assessment or other evidence presented to committee (randomized trials, observational studies, case series, expert opinion);

The amount of evidence (sparse to many number of evidence or events or individuals studied);

Consistency of evidence (results vary or largely similar); Recency (timeliness of information); Directness of evidence (link between technology and outcome); Relevance of evidence (applicability to agency program and clients); Bias (likelihood of conflict of interest or lack of safeguards).

Sufficiency or insufficiency of the evidence is a judgment of each clinical committee member and correlates closely to the GRADE confidence decision.

Not Confident Confident

Appreciable uncertainty exists. Further information is needed or further information is likely to change confidence.

Very certain of evidentiary support. Further information is unlikely to change confidence

3. Factors for Consideration - Importance

At the end of discussion a vote is taken on whether sufficient evidence exists regarding the technology’s safety, effectiveness, and cost. The committee must weigh the degree of importance that each particular key factor and the evidence that supports it has to the policy and coverage decision. Valuing the level of importance is factor or outcome specific but most often include, for areas of safety, effectiveness, and cost:

4 Based on GRADE recommendation: http://www.gradeworkinggroup.org/FAQ/index.htm UH

http://www.gradeworkinggroup.org/FAQ/index.htmU

3

Risk of event occurring; The degree of harm associated with risk; The number of risks; the burden of the condition; Burden untreated or treated with alternatives; The importance of the outcome (e.g. treatment prevents death vs. relief of symptom); The degree of effect (e.g. relief of all, none, or some symptom, duration, etc.); Value variation based on patient preference.

Clinical Committee Findings and Decisions

Efficacy Considerations What is the evidence that use of the technology results in more beneficial, important health

outcomes? Consider: o Direct outcome or surrogate measure o Short term or long term effect o Magnitude of effect o Impact on pain, functional restoration, quality of life o Disease management

What is the evidence confirming that use of the technology results in a more beneficial outcome, compared to no treatment or placebo treatment?

What is the evidence confirming that use of the technology results in a more beneficial outcome, compared to alternative treatment?

What is the evidence of the magnitude of the benefit or the incremental value?

Does the scientific evidence confirm that use of the technology can effectively replace other technologies or is this additive?

For diagnostic tests, what is the evidence of a diagnostic tests’ accuracy? o Does the use of the technology more accurately identify both those with the condition being

evaluated and those without the condition being evaluated? Does the use of the technology result in better sensitivity and better specificity?

Is there a tradeoff in sensitivity and specificity that on balance the diagnostic technology is thought to be more accurate than current diagnostic testing?

Does use of the test change treatment choices?

Safety What is the evidence of the effect of using the technology on significant morbidity?

o Frequent adverse effect on health, but unlikely to result in lasting harm or be life-threatening, or; o Adverse effect on health that can result in lasting harm or can be life-threatening?

Other morbidity concerns?

Short term or direct complication versus long term complications?

What is the evidence of using the technology on mortality – does it result in fewer adverse non-fatal outcomes?

4

Cost Impact Do the cost analyses show that use of the new technology will result in costs that are greater,

equivalent or lower than management without use of the technology?

Overall What is the evidence about alternatives and comparisons to the alternatives?

Does scientific evidence confirm that use of the technology results in better health outcomes than management without use of the technology?

Next Step: Cover or No Cover If not covered, or covered unconditionally, the Chair will instruct staff to write a proposed findings and decision document for review and final adoption at the following meeting.

Next Step: Cover with Conditions If covered with conditions, the Committee will continue discussion. 1) Does the committee have enough information to identify conditions or criteria?

Refer to evidence identification document and discussion.

Chair will facilitate discussion, and if enough members agree, conditions and/or criteria will be identified and listed.

Chair will instruct staff to write a proposed findings and decision document for review and final adoption at next meeting.

2) If not enough or appropriate information, then Chair will facilitate a discussion on the following:

What are the known conditions/criteria and evidence state

What issues need to be addressed and evidence state The chair will delegate investigation and return to group based on information and issues identified. Information known but not available or assembled can be gathered by staff ; additional clinical questions may need further research by evidence center or may need ad hoc advisory group; information on agency utilization, similar coverage decisions may need agency or other health plan input; information on current practice in community or beneficiary preference may need further public input. Delegation should include specific instructions on the task, assignment or issue; include a time frame; provide direction on membership or input if a group is to be convened. Clinical Committee Evidence Votes

First Voting Question The HTCC has reviewed and considered the technology assessment and information provided by the administrator, reports and/or testimony from an advisory group, and submissions or comments from the public. The committee has given greatest weight to the evidence it determined, based on objective factors, to be the most valid and reliable.

5

HEALTH TECHNOLOGY EVIDENCE IDENTIFICATION

Discussion Document: What are the key factors and health outcomes and what evidence is there? (Applies to the population in the PICO for this review)

Safety Outcomes Importance of Outcome

Safety Evidence / Confidence in Evidence

Morbidity/adverse events from devices

Mortality

Efficacy – Effectiveness Outcomes Importance of Outcome Efficacy / Effectiveness Evidence

Achieving target HbA1c level

Mean change HbA1c

Hypoglycemic events (acute)

Vision loss

Kidney failure

Peripheral neuropathy

Coronary artery disease

Cerebrovascular disease

Fetal outcomes

Caesarean section rates

Acute episodes hyperglycemia

Acute episodes diabetic ketoacidosis

Quality of life Pregnancy related outcomes

Gestational age Birth weight Large for gestational age Neonatal hypoglycemia Miscarriage Perinatal mortality Caesarean section HbA1c %

Cost Outcomes Importance of Outcome Cost Evidence

Costs of testing Cost effectiveness

6


Special Population / Considerations Outcomes

Importance of Outcome

Special Populations/ Considerations Evidence

Baseline HbA1c

Age

% CGM time<70 mg/dL

SMBG frequency

Education level

Hypoglycemia unawareness score

Diabetes numeracy score

Hypoglycemia fear total score

Clinical site

7


For Safety: Is there sufficient evidence that the technology is safe for the indications considered?

Unproven (no)

Less (yes)

Equivalent (yes)

More in some (yes) More in all

For Efficacy/Effectiveness: Is there sufficient evidence that the technology has a meaningful impact on patients and patient care?

Unproven (no)

Less (yes)

Equivalent (yes)


For Cost Outcomes/Cost-Effectiveness: Is there sufficient evidence that the technology is cost-effective for the indications considered?

Unproven (no)

Less (yes)

Equivalent (yes)


8


Discussion Based on the evidence vote, the committee may be ready to take a vote on coverage or further discussion may be warranted to understand the differences of opinions or to discuss the implications of the vote on a final coverage decision.

Evidence is insufficient to make a conclusion about whether the health technology is safe, efficacious, and cost-effective;

Evidence is sufficient to conclude that the health technology is unsafe, ineffectual, or not cost-effective

Evidence is sufficient to conclude that the health technology is safe, efficacious, and cost-effective for all indicated conditions;

Evidence is sufficient to conclude that the health technology is safe, efficacious, and cost-effective for some conditions or in some situations

A straw vote may be taken to determine whether, and in what area, further discussion is necessary.

Second Vote Based on the evidence about the technologies’ safety, efficacy, and cost-effectiveness, it is _____Not Covered _____ Covered Unconditionally _____ Covered Under Certain Conditions

Discussion Item Is the determination consistent with identified Medicare decisions and expert guidelines, and if not, what evidence is relied upon.

Next Step: Proposed Findings and Decision and Public Comment At the next public meeting the committee will review the proposed findings and decision and consider any public comments as appropriate prior to a vote for final adoption of the determination.

1) Based on public comment was evidence overlooked in the process that should be considered?

2) Does the proposed findings and decision document clearly convey the intended coverage determination based on review and consideration of the evidence?

Next Step: Final Determination Following review of the proposed findings and decision document and public comments: Final Vote Does the committee approve the Findings and Decisions document with any changes noted in discussion? If yes, the process is concluded. If no, or an unclear (i.e., tie) outcome Chair will lead discussion to determine next steps.

9


Medicare and Coverage Guidelines

[From page 54 of the Final Evidence Report]

Medicare Medicare does not have an NCD on CGM systems; however there is an NCD on home blood glucose monitors. These and related accessories and supplies are considered medically necessary and are covered as long as certain criteria are met by the patient or the patients’ care giver. CMS updated their policy on CGM devices in a ruling (CMS Ruling 1682R) published on January 12, 2017. This ruling separated CGM devices into therapeutic and non-therapeutic devices, and allows for therapeutic devices to be considered as durable medical equipment (DME). Therapeutic devices are those used as a replacement for fingerstick BG testing for diabetes treatment decisions (i.e. used as a primary system and not as an adjunct) and must meet five criteria used to classify DMEs. The ruling does not establish CGM broadly as medically necessary but does allow for claim-by-claim payment for devices approved for therapeutic uses.

Guidelines

[From page 27-35 of Final Evidence Report]

Table 2. Summary of clinical guidelines

Guideline Evidence Base Recommendation Rating/Strength of Recommendation

American Diabetes Association (ADA)* 7 Standards of Medical Care in Diabetes (2017)

1 meta-analysis 4 RCTs 1 registry study 3 studies, type NR

CGM may be a useful tool in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes. Individual readiness should be assessed prior to prescribing CGM. Robust diabetes education, training, and support are required for optimal CGM implementation and ongoing use.

Adult population CGM, when used properly and in conjunction with intensive insulin regimens, is a useful tool for lowering A1C levels in selected adults (aged 25 years or older) with T1DM. People who have been using CGM successfully should have continued access after they turn 65 years old.

C† E† E† A† E†

10



Pediatric population CGM may be helpful for lowering A1C levels in children, teens, and younger

adults.

B†

Joslin Diabetes Center and Joslin Clinic (Shahar et al.) 140 Clinical guideline for adults with diabetes (2015, revised 2017)

1 RCT 2 studies, type NR

For patients using RT-CGM to treat hypoglycemia, blood glucose levels should be checked 15 minutes post treatment using a finger stick and not the sensor reading. CGM can be considered if the patient has a history of severe recurrent hypoglycemia or hypoglycemia unawareness.

1B‡ NR

Peters et al. 118 Diabetes Technology—Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline (2016)

T1DM in adults 7 studies, type NR T2DM in adults 1 RCT 1 study, type NR

RT-CGM is recommended for adults patients with T1DM who have A1C levels above target and who are willing and able to use devices on a nearly daily basis. RT-CGM is recommended for adult patients with well-controlled T1DM who are willing and able to use devices on a nearly daily basis. It is suggested that short-term, intermittent RT-CGM is used in adult patients with T2DM (not on prandial insulin) who have A1C levels at 7% or greater and are willing and able to use the device. It is suggested that adults with T1DM and T2DM who use CSII and CGM receive education, training, and ongoing support to help achieve and maintain individualized glycemic goals.

1, A§ 1, A§ 2, C§ Ungraded Good Practice Statement

Handelsman et al. 60 American Association of Clinical Endocrinologists and American College of Endocrinology—Clinical Practice Guidelines for Developing a Diabetes

2 RCTs CGM should be considered for patients with T1DM and T2DM on intensive insulin therapy to improve A1C levels and reduce hypoglycemia. CGM may benefit patients not taking insulin.

Grade B, BEL 2** Grade D, BEL 4**

11



Mellitus Comprehensive Care Plan (2015)

Blumer et al. 21 Diabetes and pregnancy: an Endocrine Society clinical practice guideline (2013)

NR CGM is suggested for use during pregnancy in women with overt or gestational diabetes when self-monitored blood glucose levels (or HbA1C values in women with overt diabetes) are not sufficient to assess glycemic control

2++††

Klonoff et al.‡‡ 86 Continuous Glucose Monitoring: An Endocrine Society Clinical Practice Guideline (2011)

T1DM in children and adolescents 3 RCTs 11 studies, type NR T1DM in adults 2 RCT 5 studies, type NR

RT-CGM is recommended for children and adolescents with T1DM who have achieved HbA1c levels below 7.0%. RT-CGM is recommended for children and adolescents with T1DM with T1DM who have HbA1c levels of 7.0% or higher who are able to use devices on a nearly daily basis. No recommendations are made for or against the use of RT-CGM in children with T1DM who are less than 8 years old.

1, A§ 1, B§ NA§

NICE 112 Integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system) (2016)

NR The MiniMed Paradigm Veo system is recommended as an option for managing blood glucose levels in people with T1DM only if:

They have episodes of disability hypoglycemia despite optimal management with CSII and

The company arranges to collect, analyze, and publish data on the use of the MiniMed Paradigm Veo system

The MiniMed Paradigm Veo system should be used under the supervision of a trained multidisciplinary team who are experienced in CSII and CGM for managing T1DM only if the person or their carer:

NR

12



Agrees to use the sensors for at least 70% of the time

Understands how to use it and is physically able to use the system and

Agrees to use the system while having a structured education program on diet and lifestyle, and counselling

People who start using the MiniMed Paradigm Veo system should only continue use it if there is a sustained decrease in the number of hypoglycemic episodes. There is insufficient evidence for the Vibe and G4 PLATINUM CGM to support routine adoption in the National Health Service for managing blood glucose levels in people with T1DM.

NICE (National Clinical Guideline Centre) 108 Type 1 diabetes in adults: diagnosis and management (2015)

NR Do not offer RT-CGM routinely in adults with T1DM. RT-CGM can be considered for adults with T1DM willing to commit to using at least 70% of the time and to calibrate the device as needed, and who have any of the following characteristics despite optimized use of insulin therapy and conventional BGM:

> 1 episode of severe hypoglycemia per year with no obviously preventable precipitating cause

Complete loss of awareness of hypoglycemia

Frequent (>2) episodes per week of asymptomatic hypoglycemia that causes problems with daily activities

NR

13



Extreme fear of hypoglycemia

Hyperglycemia (HbA1c levels of 9% or higher) that persists despite testing at least 10 times per day. RT-CGM should only be continued if HbA1c can be sustained at or below 7% and/or there has been a fall in HbA1c levels of 2.5% or more

Adults with T1DM using RT-CGM should use the principles of flexible insulin therapy with either a multiple daily injection insulin regimen or CSII therapy. RT-CGM should be provided by a center with expertise in its use, as a part of strategies to optimize a person’s HbA1c levels and reduce frequency of hypoglycemic episodes.

National Collaborating Centre For Women and Children’s Health 109 Diabetes (type 1 and type 2) in children and young people: diagnosis and management (2015)

NR Offer ongoing RT-CGM with alarms to children and young people with T1DM who have at least 1 of the following:

Frequent severe hyperglycemia

Impaired awareness of hypoglycemia associated with adverse consequences (e.g. seizures or anxiety)

Inability to recognize or communicate about symptoms of hypoglycemia (e.g. cognitive or neurological disabilities)

Offer ongoing RT-CGM for:

Neonates, infants, and pre-school children

Children and young people who have undertaken high levels of physical activity

NR

14



Children and young people who have comorbidities or who are receiving treatments that can make blood glucose control difficult

CGM can be considered to help improve blood glucose control in children and young people who continue to have hyperglycemia despite insulin adjustment and additional support.

National Collaborating Centre For Women and Children’s Health 110 Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period (2015)

NR Do not offer CGM routinely to pregnant women with diabetes. CGM can be considered for pregnant women on insulin therapy if one of the following applies:

Problematic severe hypoglycemia (with or without impaired awareness of hypoglycemia)

Unstable blood glucose levels (to minimize variability)

To gain information about variability in blood glucose levels

Ensure that support is available for pregnant women who are using continuous glucose monitoring from a member of the joint diabetes and antenatal care team with expertise in its use.

NR

Wright et al. 161 A Practical Approach to the Management of Continuous Glucose Monitoring (CGM) / Real-Time Flash Glucose Scanning (FGS) in Type 1 Diabetes Mellitus in Children and Young

1 SR 2 RCTs 13 studies, type NR

Continuous CGM can be considered for any patient irrespective of age, sex, socioeconomic status, ethnic, or educational background who meet NICE criteria§§. Continuous CGM can be considered in children on CSII or MDI therapy.

B*** A*** B***

15



People Under 18 Years (2017)

Continuous CGM with alarms should be considered in any child of any age who has had a hypoglycemic seizure. Continuous CGM with alarms should be considered in all young children. Continuous CGM with alarms should be considered in all children of any age with neurodevelopmental or cognitive problems that impair their ability either to recognize or respond to hypoglycemia. CGM with alarms should be considered in frequent hypoglycemia and in nocturnal hypoglycemia. CGM with alarms should be considered in situations with individuals who have unawareness of hypoglycemia. CGM with alarms should be considered in individuals where anxiety or fear of hypoglycemia is high. CGM can be considered for improving diabetes control in children and young people by reducing HbA1c and/or reducing the time spent in hypoglycemia, with any HbA1c < 10%. CGM is not recommended for use to reduce HbA1c or hypoglycemia in children with HbA1c > 10%.

A*** D*** B*** B*** D*** B*** D***

Choudhary et al. 31 Evidence-Informed Clinical Practice Recommendations for Treatment of Type 1 Diabetes Complicated by Problematic Hypoglycemia (2015)

2 SRs 4 RCTs 1 observational study 4 studies, type NR

CSII or CGM should be added to the treatment regimen of patient’s with T1DM and problematic hypoglycemia if glycemic and hypoglycemia targets are not met though an education or hypoglycemia-specific education program.

NR

Working Group of the Clinical Practice

NR CGM can be used as an instrument to improve or maintain metabolic

A***

16



Guideline on Diabetes Mellitus Type 1 159 Clinical practice guidelines for diabetes type 1 (2012)

control in patients motivated and trained in intensive care. However, CGM is not recommended for universal use for people with T1DM.

BGM, blood glucose monitoring; CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion; HbA1c, hemoglobin A1c (glycated hemoglobin); MDI, Multiple Daily Injection; NICE, National Institute for Health and Care Excellence; NR, not reported; RCT, randomized controlled trial; RT-CGM, real-time continuous glucose monitoring; SR, systematic review; T1DM, Type 1 diabetes mellitus; T2DM, Type 2 diabetes mellitus * Chamberlain 2016 details the ADA Standards of Medical Care from 2016. The paper supports the use of CGM for the reduction of severe hypoglycemia risk but gives no additional recommendations for CGM †ADA evidence-grading systems for “Standards of Medical Care in Diabetes”

A: Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including Evidence from a well-conducted multicenter trial

Evidence from a meta-analysis that incorporated quality ratings in analysis Compelling nonexperimental evidence, i.e. “all or none” rule developed by the Centre for Evidence-Based Medicine at the University of Oxford. Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including

Evidence from well-conducted trials at one or more institutions

Evidence from meta-analysis that incorporated quality ratings in the analysis

B: Supportive evidence from well-conducted cohort studies Evidence from a well-conducted prospective cohort study or registry

Evidence from a well-conducted meta-analysis of cohort studies

Supportive evidence from a well-conducted case-control study C: Supportive evidence from poorly controlled or uncontrolled studies

Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results

Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls)

Evidence from case series or case reports

Conflicting evidence with the weight of evidence supporting the recommendation E: Expert consensus or clinical experience

‡ Strength of recommendation grading: 1A: strong recommendation and high quality of evidence 1B: Strong recommendation and moderate quality of evidence 1C: Strong recommendation and low quality of evidence 2A: Weak recommendation and high quality of evidence 2B: Weak recommendation and moderate quality of evidence 2C: Weak recommendation and low quality of evidence

§GRADE Strength of Recommendation: 1: Strong for an intervention 2: Weak for an intervention 3: Weak against an intervention 4: Strong against an intervention

GRADE Quality of Evidence rating: A: High quality of evidence B: Moderate quality of evidence C: Low quality of evidence D: Very low quality of evidence

** Strength of recommendation grading:

17


A: Strong B: Intermediate C: Weak D: Not evidence based

Best evidence level (BEL) grading: 1: Meta-analysis of randomized controlled trials (MRCT) OR randomized controlled trials (RCT) 2: Meta-analysis of nonrandomized prospective or case-controlled trials (MNRCT) OR nonrandomized controlled trial OR prospective cohort study (NRCT) OR prospective cohort study (PCS) OR retrospective case-control study (RCCS) 3: Cross-sectional study (CSS) OR surveillance study (SS) OR consecutive case series (CCS) OR single case reports (SCR) 4: No evidence; based on theory, opinion, consensus, review, or preclinical study (NE)

††Quality of evidence and strength of recommendation grading: Quality of evidence:

+ denotes very low quality evidence ++ denotes low quality evidence +++ denotes moderate quality evidence ++++ denotes high quality evidence

Strength of recommendation: 1-indicates a strong recommendation 2-indicates a weak recommendation

‡‡Recommendations for adult populations were not included because updated guidelines from the Endocrine Society for adult populations are in Peters et al. §§NICE criteria was stated as patients with the following indications: hypoglycemic seizures, frequent severe hypoglycemia, impaired awareness of hypoglycemia, anxiety regarding hypoglycemia, inability to recognize hypoglycemia due to cognitive or neurological disabilities, young children who may not be able to recognize and respond, patients undertaking high levels of physical activity, to reduce HbA1c, to improve glycemic control, or to reduce glycemic variation ***Strength of recommendation grading:

A: At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or A body of evidence consisting principally or studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results. B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++ D: Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+

Table 3. Summary of consensus statements

Consensus statement Evidence Base Recommendation Rating/Strength of Recommendation

Danne et al. International Consensus on Use of Continuous Glucose Monitoring (2017)

Type 1 12 studies, type NR Type 2 3 studies, type NR Gestational diabetes 1 study, type NR

CGM should be considered in conjuction with HbA1c for glycemic status assessment nd therapy adjustment in all patients with type 1 and patients with type 2 diabetes treated with intesnsive insulin therapy who are not achieving glucose targets, especially if the patient is experiencing problematic hypoglycemia Al patients should receive training in how to interpret and respond to their glucose data. Patient education and training for CGM

NR

18



should utilized standardized programs with follow-up to improve adherence and facilitate appropriate use of data and diabetes therapies. CGM data should be used to assess hypoglycemia and glucose variability

Bailey et al. 12 American Association of Clinical Endocrinologists and American College of Endocrinology 2016 Outpatient Glucose Monitoring Consensus Statement (2016) Fonseca et al.* 50 Continuous Glucose Monitoring: A Consensus Conference of the American Association of Clinical Endocrinologists and American College of Endocrinology (2016)

T1DM 1 study, type NR 1 nonrandomized study 2 RCT T2DM 2 RCTs Gestational Diabetes 1 study, type NR 3 RCTs

CGM should be available to all insulin-using patients regardless of diabetes type, although data on CGM is limited in patients with T2DM receiving insulin/sulfonylureas or glinides. No recommendation can be made for CGM in patients with T2DM that have a low risk of hypoglycemia

Adult population CGM is recommended in adults with T1DM, particularly in patients with history of severe hypoglycemia, hypoglycemia unawareness, and to assist in the correction of hyperglycemia in patients not at goal.

Pediatric population

CGM is recommended in children with pediatric T1DM, particularly in patients with history of severe hypoglycemia, hypoglycemia unawareness, and to assist in the correction of hyperglycemia in patients not at goal. More in-depth training and more frequent follow-up is recommended.

Pregnant population CGM can be used during pregnancy as a teaching tool, to evaluate glucose patterns, and to fine-tune insulin dosing.

NR

19



CGM in pregnancy can supplement BGM particularly to monitor nocturnal hypoglycemia or hyperglycemia and postprandial hyperglycemia.

Rewers et al. 128 ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Assessment and monitoring of glycemic control in children and adolescents with diabetes (2014)

2 RCTs 8 studies, type NR

CGM devices are becoming available that may particularly benefit those with hypoglycemic unawareness.

A†

Kesavadev et al. 83 Consensus guidelines for glycemic monitoring in type 1/type 2 & GDM (2014)

T1DM in adults and adolescents 2 studies, type NR T1DM in youth 5 studies, type NR

CGM may be a supplemental tool to SMBG in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes.

Adult population CGM in conjunction with intensive insulin regimens can be useful in lowering A1C in selected adults (age ≥25 years) with type 1 diabetes.

Pediatric population CGM may be helpful in children, teens, and younger adults in lowering A1C levels. CGM is recommended in children and adolescents with T1DM who have achieved HbA1c levels less than 7.0%. CGM is recommended in youth with T1DM who have HbA1c levels 7.0% or higher and are able to use the device on a near-daily basis.

Pregnant population Pregnant patients with T1DM should be offered CGM

D‡ A‡ C‡ D‡ D‡ Rating NR

20



Scaramuzza et al. 135 Recommendations for self-monitoring in pediatric diabetes: a consensus statement by the ISPED (2013)

2 SRs 3 RCTs 9 studies, type NR

Patients should fulfill the following criteria to be a candidate for CGM:

Children with no awareness of hypoglycemia or frequent episodes of severe hypoglycemia

Children and adolescents with impaired metabolic control (HbA1c > 8.5%) on intensive insulin therapy

CGM could be helpful in the following circumstances:

To improve metabolic control regardless of HbA1c value

To reduce SMBG measurements, especially if > 10 times per day

To help patients undergoing competitive sports

To start insulin pump therapy

NR

BGM, blood glucose monitoring; CGM, continuous glucose monitoring; GDM, gestational diabetes mellitus; HbA1c, hemoglobin A1c (glycated hemoglobin); ISPAD, International Society for Pediatric and Adolescent Diabetes; ISPED, Italian Society of Pediatric Endocrinology and Diabetology; NR, not reported; RCT, randomized controlled trial; SMBG, self-monitoring blood glucose; SR, systematic review; T1DM, Type 1 diabetes mellitus; T2DM, Type 2 diabetes mellitus *Fonseca et al. was associated with the same consensus conference as Bailey et al; emphasis for information on recommendations was placed on Bailey et al. while Fonseca et al. was used for background information and context. † System for rating strength of recommendation was not reported ‡ Strength of recommendation grading:

A: Type of evidence supporting recommendation is based on randomized controlled trials, meta-analyses, or systematic reviews B: Type of evidence supporting recommendation is based on non-randomized controlled trials or uncontrolled randomized clinical trials C: Type of evidence supporting recommendation is based on observational trials or evidence based reviews or case studies D: Type of evidence supporting recommendation is based on opinion of expert panel

brent e. wisse, md - washington state health care authority · 1/19/2018 · brent e. wisse, md,...

Documents